Abstract
Pregnancy losses negatively affect the cattle industry, impacting economic indices and consequently the entire production chain. Early embryonic failure has been an important challenge in the embryo industry because proper identification of embryo death at the beginning of gestation is difficult. This review aimed to provide a better understanding on reproductive failure and the relationship between early embryonic loss and different reproductive biotechniques. This review also considers insights and possible strategies for reducing early embryonic loss. The strategies addressed are as follows: i) great impact of rigorous embryo evaluation on reducing embryo losses; ii) selection of recipients at the time of transfer, taking into account health and nutritional status, and classification of the corpus luteum using ultrasound, either in area or vascularization; and iii) paternal effect as one of the factors that contribute to pregnancy losses, with a focus on embryo transfer.
Keywords:
embryo mortality; embryo classification; recipient selection; evaluation of corpus luteum; paternal effect
Introduction
Cattle farming is of great economic importance both globally and nationally. Despite the importance of cattle farming, reproductive failure remains a substantially managerial and economic challenge. Globally, reproductive inefficiency are estimated to cost the cattle industry more than US $ 1 billion annually (USDA, 2009USDA. NAHMS dairy 2007 part IV: reference of dairy cattle health and management practices in the United States. Fort Collins: USDA–APHIS–VS–CEAH–NAHMS; 2009. p. 33-43., 2010USDA. NAHMS Beef 2007-2008. Fort Collins, CO: USDA–APHIS–VS–CEAH–NAHMS; 2010.). Although several factors influence reproductive efficiency, the main cause is gestational loss (Perkel et al., 2015Perkel KJ, Tscherner A, Merrill C, Lamarre J, Madan P. The ART of selecting the best embryo: a review of early embryonic mortality and bovine embryo viability assessment methods. Mol Reprod Dev. 2015;82(11):822-38. http://doi.org/10.1002/mrd.22525. PMid:26184077.
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), which reinforces the need for a greater understanding of the subject.
The period of gestational loss in cattle is generally classified as early embryonic mortality (EEM), when it occurs between fertilization and 28 to 32 days after fertilization, late embryonic mortality (LEM) when it occurs between days 28 and 30 and up to 45 days, early fetal mortality when it occurs between days 45 and 60, and late fetal mortality from day 60 until the end of gestation (Smith et al., 2022Smith BD, Poliakiwski B, Polanco O, Singleton S, de Melo GD, Muntari M, Oliveira Filho RV, Pohler KG. Decisive points for pregnancy losses in beef cattle. Reprod Fertil Dev. 2022;35(2):70-83. http://doi.org/10.1071/RD22206. PMid:36592980.
http://doi.org/10.1071/RD22206...
; Albaaj et al., 2023Albaaj A, Durocher J, LeBlanc SJ, Dufour S. Meta-analysis of the incidence of pregnancy losses in dairy cows at different stages to 90 days of gestation. JDS Commun. 2023;4(2):144-8. http://doi.org/10.3168/jdsc.2022-0278. PMid:36974208.
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). In cattle, gestational losses are more prevalent in the embryonic than in the fetal stages (Santos et al., 2004Santos JEP, Thatcher WW, Chebel RC, Cerri RLA, Galvão KN. The effect of embryonic death rates in cattle on the efficacy of estrus synchronization programs. Anim Reprod Sci. 2004;82–83:513-35. http://doi.org/10.1016/j.anireprosci.2004.04.015. PMid:15271477.
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), have variable causes (Diskin and Morris, 2008Diskin MG, Morris DG. Embryonic and early foetal losses in cattle and other ruminants. Reprod Domest Anim. 2008;43(Suppl 2):260-7. http://doi.org/10.1111/j.1439-0531.2008.01171.x. PMid:18638133.
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; Farin, Piedrahita, Farin, 2006Farin PW, Piedrahita JA, Farin CE. Errors in development of fetuses and placentas from in vitro-produced bovine embryos. Theriogenology. 2006;65(1):178-91. http://doi.org/10.1016/j.theriogenology.2005.09.022. PMid:16266745.
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; Cheng et al., 2016Cheng Z, Abudureyimu A, Oguejiofor CF, Ellis R, Barry AT, Chen X, Anstaett OL, Brownlie J, Wathes DC. BVDV alters uterine prostaglandin production during pregnancy recognition in cows. Reproduction. 2016;151(6):605-14. http://doi.org/10.1530/REP-15-0583. PMid:26952097.
http://doi.org/10.1530/REP-15-0583...
; Pohler et al., 2016Pohler KG, Peres RFG, Green JA, Graff H, Martins T, Vasconcelos JLM, Smith MF. Use of bovine pregnancy-associated glycoproteins to predict late embryonic mortality in postpartum Nelore beef cows. Theriogenology. 2016;85(9):1652-9. http://doi.org/10.1016/j.theriogenology.2016.01.026. PMid:26928645.
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; Abdalla et al., 2017Abdalla H, Elghafghuf A, Elsohaby I, Nasr MA. Maternal and non-maternal factors associated with late embryonic and early fetal losses in dairy cows. Theriogenology. 2017;100:16-23. http://doi.org/10.1016/j.theriogenology.2017.04.005. PMid:28708529.
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) and are often undetermined (Santos et al., 2004Santos JEP, Thatcher WW, Chebel RC, Cerri RLA, Galvão KN. The effect of embryonic death rates in cattle on the efficacy of estrus synchronization programs. Anim Reprod Sci. 2004;82–83:513-35. http://doi.org/10.1016/j.anireprosci.2004.04.015. PMid:15271477.
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).
A summary of the incidence of gestational losses has been reported in specific meta-analyses of dairy cattle (Albaaj et al., 2023Albaaj A, Durocher J, LeBlanc SJ, Dufour S. Meta-analysis of the incidence of pregnancy losses in dairy cows at different stages to 90 days of gestation. JDS Commun. 2023;4(2):144-8. http://doi.org/10.3168/jdsc.2022-0278. PMid:36974208.
http://doi.org/10.3168/jdsc.2022-0278...
) and beef cattle (Reese et al., 2020Reese ST, Franco GA, Poole RK, Hood R, Fernadez Montero L, Oliveira Filho RV, Cooke RF, Pohler KG. Pregnancy loss in beef cattle: A meta-analysis. Anim Reprod Sci. 2020;212:106251. http://doi.org/10.1016/j.anireprosci.2019.106251. PMid:31864492.
http://doi.org/10.1016/j.anireprosci.201...
); however, several factors, including the animal's production category, stage of pregnancy, and environmental conditions, influence gestational losses (Diskin et al., 2016Diskin MG, Waters SM, Parr MH, Kenny DA. Pregnancy losses in cattle: potential for improvement. Reprod Fertil Dev. 2016;28(1-2):83-93. http://doi.org/10.1071/RD15366. PMid:27062877.
http://doi.org/10.1071/RD15366...
; Fernandez-Novo et al., 2020Fernandez-Novo A, Fargas O, Loste JM, Sebastian F, Perez-Villalobos N, Pesantez-Pacheco JL, Patron-Collantes R, Astiz S. Pregnancy loss (28-110 days of pregnancy) in holstein cows: a retrospective study. Animals (Basel). 2020;10(6):925. http://doi.org/10.3390/ani10060925. PMid:32466555.
http://doi.org/10.3390/ani10060925...
).
In dairy cattle, an average of 27% of gestational loss occurs in the early embryonic period (Albaaj et al., 2023Albaaj A, Durocher J, LeBlanc SJ, Dufour S. Meta-analysis of the incidence of pregnancy losses in dairy cows at different stages to 90 days of gestation. JDS Commun. 2023;4(2):144-8. http://doi.org/10.3168/jdsc.2022-0278. PMid:36974208.
http://doi.org/10.3168/jdsc.2022-0278...
) and can reach 40% in cows with moderate production (Diskin et al., 2016Diskin MG, Waters SM, Parr MH, Kenny DA. Pregnancy losses in cattle: potential for improvement. Reprod Fertil Dev. 2016;28(1-2):83-93. http://doi.org/10.1071/RD15366. PMid:27062877.
http://doi.org/10.1071/RD15366...
), 12% (ranging from 3.5 to 25%; Wiltbank, et al., 2016Wiltbank MC, Baez GM, Garcia-Guerra A, Toledo MZ, Monteiro PL, Melo LF, Ochoa JC, Santos JE, Sartori R. Pivotal periods for pregnancy loss during the first trimester of gestation in lactating dairy cows. Theriogenology. 2016;86(1):239-53. http://doi.org/10.1016/j.theriogenology.2016.04.037. PMid:27238438.
http://doi.org/10.1016/j.theriogenology....
; Santos et al., 2004Santos JEP, Thatcher WW, Chebel RC, Cerri RLA, Galvão KN. The effect of embryonic death rates in cattle on the efficacy of estrus synchronization programs. Anim Reprod Sci. 2004;82–83:513-35. http://doi.org/10.1016/j.anireprosci.2004.04.015. PMid:15271477.
http://doi.org/10.1016/j.anireprosci.200...
) in the late embryonic period, 7% in the early fetal period, and 2% in the late fetal period (Albaaj et al., 2023). In beef cattle, an average of 28.4% of gestational losses occurred up to day 7 of gestation, 3.9% occurred between days 7 and 16, and 15.6% occurred between days 16 and 32, totaling 47.9% of losses in the early embryonic period. Therefore, 6% of gestational losses occur after the first month of gestation (Reese et al., 2020Reese ST, Franco GA, Poole RK, Hood R, Fernadez Montero L, Oliveira Filho RV, Cooke RF, Pohler KG. Pregnancy loss in beef cattle: A meta-analysis. Anim Reprod Sci. 2020;212:106251. http://doi.org/10.1016/j.anireprosci.2019.106251. PMid:31864492.
http://doi.org/10.1016/j.anireprosci.201...
) and can vary between 5 and 20% (Perry et al., 2005Perry GA, Smith MF, Lucy MC, Verde JA, Parques TE, MacNeil MD, Roberts AJ, Geary TW. Relationship between follicle size at insemination and pregnancy success. Proc Natl Acad Sci USA. 2005;102(14):5268-73. http://doi.org/10.1073/pnas.0501700102. PMid:15795381.
http://doi.org/10.1073/pnas.0501700102...
; Wiltbank et al., 2016Wiltbank MC, Baez GM, Garcia-Guerra A, Toledo MZ, Monteiro PL, Melo LF, Ochoa JC, Santos JE, Sartori R. Pivotal periods for pregnancy loss during the first trimester of gestation in lactating dairy cows. Theriogenology. 2016;86(1):239-53. http://doi.org/10.1016/j.theriogenology.2016.04.037. PMid:27238438.
http://doi.org/10.1016/j.theriogenology....
). Although the periods investigated vary among studies, the results provide a summary of the percentages of cattle losses and highlight their biological and economic challenges, especially concerning embryonic losses. Therefore, it is important to discuss the relationship between embryonic losses in different reproductive biotechniques (Baruselli et al., 2010Baruselli PS, Ferreira RM, Sá MF Fo, Nasser LFT, Rodrigues CA, Bo GA. Bovine embryo transfer recipient synchronisation and management in tropical environments. Reprod Fertil Dev. 2010;22(1):67-74. http://doi.org/10.1071/RD09214. PMid:20003847.
http://doi.org/10.1071/RD09214...
; Reese et al; Hansen, 2020Hansen PJ. The incompletely fulfilled promise of embryo transfer in cattle-why aren’t pregnancy rates greater and what can we do about it? J Anim Sci. 2020;98(11):skaa288. http://doi.org/10.1093/jas/skaa288. PMid:33141879.
http://doi.org/10.1093/jas/skaa288...
).
In addition, because the highest percentage of gestational losses in cattle occurs in the embryonic phase, detecting these losses, especially by diagnosing them at 30 and 60 days, offers an opportunity for timely reproduction and reduces the costs associated with this source of reproductive inefficiency (Reese et al., 2020Reese ST, Franco GA, Poole RK, Hood R, Fernadez Montero L, Oliveira Filho RV, Cooke RF, Pohler KG. Pregnancy loss in beef cattle: A meta-analysis. Anim Reprod Sci. 2020;212:106251. http://doi.org/10.1016/j.anireprosci.2019.106251. PMid:31864492.
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). Currently, there are several techniques for detecting gestational status, such as transrectal ultrasound, circulating concentrations of progesterone, circulating placental products (pregnancy-associated glycoproteins (PAGs) and microRNAs), and interferon-stimulating gene expression in peripheral blood leukocytes (Ealy, Seekford, 2019Ealy AD, Seekford ZK. Symposium review: predicting pregnancy loss in dairy cattle. J Dairy Sci. 2019;102(12):11798-804. http://doi.org/10.3168/jds.2019-17176. PMid:31587904.
http://doi.org/10.3168/jds.2019-17176...
).
Transrectal B-mode ultrasound is a highly accurate method and widely used for gestational diagnosis. However, its use is limited to after–27th-28th day of gestation (Nation et al., 2003Nation DP, Malmo J, Davis GM, Macmillan KL. Accuracy of bovine pregnancy detection using transrectal ultrasonography at 28 to 35 days after insemination. Aust Vet J. 2003;81(1-2):63-5. http://doi.org/10.1111/j.1751-0813.2003.tb11435.x. PMid:15084014.
http://doi.org/10.1111/j.1751-0813.2003....
). Pregnancy-associated glycoproteins expressed in the third week of gestation in cattle (Wallace et al., 2015Wallace RM, Pohler KG, Smith MF, Green JA. Placental PAGs: gene origins, expression patterns, and use as markers of pregnancy. Reproduction. 2015;149(3):R115-26. http://doi.org/10.1530/REP-14-0485. PMid:25661256.
http://doi.org/10.1530/REP-14-0485...
) have also been shown to be accurate for commercial diagnosis, but are limited to the 28th day of gestation (Ribeiro et al., 2014Ribeiro ES, Bruno RGS, Farias AM, Hernández-Rivera JA, Gomes GC, Surjus R, Becker LFV, Birt A, Ott TL, Branen JR, Sasser RG, Keisler DH, Thatcher WW, Bilby TR, Santos JEP. Low doses of bovine somatotropin enhance conceptus development and fertility in lactating dairy cows. Biol Reprod. 2014;90(1):10-2. http://doi.org/10.1095/biolreprod.113.114694. PMid:24285716.
http://doi.org/10.1095/biolreprod.113.11...
; Pohler et al., 2016Pohler KG, Peres RFG, Green JA, Graff H, Martins T, Vasconcelos JLM, Smith MF. Use of bovine pregnancy-associated glycoproteins to predict late embryonic mortality in postpartum Nelore beef cows. Theriogenology. 2016;85(9):1652-9. http://doi.org/10.1016/j.theriogenology.2016.01.026. PMid:26928645.
http://doi.org/10.1016/j.theriogenology....
), and their concentrations are associated with the likelihood of maintaining pregnancy (Pohler et al., 2016Pohler KG, Peres RFG, Green JA, Graff H, Martins T, Vasconcelos JLM, Smith MF. Use of bovine pregnancy-associated glycoproteins to predict late embryonic mortality in postpartum Nelore beef cows. Theriogenology. 2016;85(9):1652-9. http://doi.org/10.1016/j.theriogenology.2016.01.026. PMid:26928645.
http://doi.org/10.1016/j.theriogenology....
). Therefore, Doppler ultrasound has been proposed as an accurate method for identifying nonpregnant females from the 20th day of pregnancy (Siqueira et al., 2013Siqueira LGB, Areas VS, Ghetti AM, Fonseca JF, Palhao MP, Fernandes CAC, Viana JHM. Color doppler flow imaging for the early detection of nonpregnant cattle at 20 days after timed artificial insemination. J Dairy Sci. 2013;96(10):6461-72. http://doi.org/10.3168/jds.2013-6814. PMid:23958005.
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; Pugliesi et al., 2014Pugliesi G, Miagawa BT, Paiva YN, França MR, Silva LA, Binelli M. Conceptus-induced changes in the gene expres¬sion of blood immune cells and the ultrasound-accessed luteal function in beef cattle: how early can we detect pregnancy? Biol Reprod. 2014;91(4):95. http://doi.org/10.1095/biolreprod.114.121525. PMid:25210129.
http://doi.org/10.1095/biolreprod.114.12...
; Melo et al., 2020Melo GD, Mello BP, Ferreira CA, Filho CASG, Rocha CC, Silva AG, Reese ST, Madureira EH, Pohler KG, Pugliesi G. Applied use of interferon-tau stimulated genes expression in polymorphonuclear cells to detect pregnancy compared to other early predictors in beef cattle. Theriogenology. 2020;152:94-105. http://doi.org/10.1016/j.theriogenology.2020.04.001. PMid:32387553.
http://doi.org/10.1016/j.theriogenology....
).
Given the importance of reproductive loss, it is necessary to develop strategies to reduce pregnancy failure. This review aimed to provide insights into possible strategies for reducing embryonic loss after embryo transfer.
Reproductive biotechniques vs. pregnancy loss
The use of biotechniques as a reproductive management tool has evolved considerably in recent decades, resulting in increased reproductive efficiency in dairy and beef cattle. Despite the increase in reproductive ability, provided to the herd through reproductive biotechniques such as artificial insemination (AI), fixed-time artificial insemination (FTAI), embryo transfer (ET), and in vitro fertilization (IVF), understanding the factors related to their success during application is necessary. In this context, pregnancy rates were obtained, mainly the rates of pregnancy loss.
Several studies have investigated the influence of in vivo and in vitro methods of embryo production and cryopreservation on pregnancy rates and embryo loss. IVP blastocysts have many characteristics that differ from those of blastocysts produced in vivo by superovulation, such as accumulation of intracellular lipids, oxygen consumption, DNA methylation, and gene expression (Burdge, Lillycrop, 2010Burdge GC, Lillycrop KA. Nutrition, epigenetics, and developmental plasticity: implications for understanding human disease. Annu Rev Nutr. 2010;30(1):315-39. http://doi.org/10.1146/annurev.nutr.012809.104751. PMid:20415585.
http://doi.org/10.1146/annurev.nutr.0128...
; Rizos et al., 2002Rizos D, Ward F, Duffy P, Boland MP, Lonergan P. Consequences of bovine oocyte maturation, fertilization or early embryo development in vitro versus in vivo: implications for blastocyst yield and blastocyst quality. Mol Reprod Dev. 2002;61(2):234-48. http://doi.org/10.1002/mrd.1153. PMid:11803560.
http://doi.org/10.1002/mrd.1153...
; Reese et al., 2020Reese ST, Franco GA, Poole RK, Hood R, Fernadez Montero L, Oliveira Filho RV, Cooke RF, Pohler KG. Pregnancy loss in beef cattle: A meta-analysis. Anim Reprod Sci. 2020;212:106251. http://doi.org/10.1016/j.anireprosci.2019.106251. PMid:31864492.
http://doi.org/10.1016/j.anireprosci.201...
; Banliat et al., 2022Banliat C, Mahé C, Lavigne R, Com E, Pineau C, Labas V, Guyonnet B, Mermillod P, Saint-Dizier M. Dynamic Changes in the Proteome of Early Bovine Embryos Developed In Vivo. Front Cell Dev Biol. 2022;21(10):863700. http://doi.org/10.3389/fcell.2022.863700. PMid:35386205.
http://doi.org/10.3389/fcell.2022.863700...
).
The reproductive failure rates in beef cattle described in a meta-analysis were 32.2%, 49.5%, and 54.6% for cows subjected to AI after the natural expression of estrus, FTAI, and ET, respectively (Reese et al., 2020Reese ST, Franco GA, Poole RK, Hood R, Fernadez Montero L, Oliveira Filho RV, Cooke RF, Pohler KG. Pregnancy loss in beef cattle: A meta-analysis. Anim Reprod Sci. 2020;212:106251. http://doi.org/10.1016/j.anireprosci.2019.106251. PMid:31864492.
http://doi.org/10.1016/j.anireprosci.201...
). Reportedly, a reduction of up to 24% in the pregnancy rate for embryos produced in vitro compared to in vivo (Farin, Crosier, Farin, 2001Farin PW, Crosier AE, Farin CE. Influence of in vitro systems on embryo survival and fetal development in cattle. Theriogenology. 2001;55(1):151-70. http://doi.org/10.1016/S0093-691X(00)00452-0. PMid:11198080.
http://doi.org/10.1016/S0093-691X(00)004...
) and 7.4% lower pregnancy rate for recipients who received cryopreserved embryos (frozen or vitrified) than fresh ones (Hansen, 2020Hansen PJ. The incompletely fulfilled promise of embryo transfer in cattle-why aren’t pregnancy rates greater and what can we do about it? J Anim Sci. 2020;98(11):skaa288. http://doi.org/10.1093/jas/skaa288. PMid:33141879.
http://doi.org/10.1093/jas/skaa288...
). The status (fresh or cryopreserved) of the embryo also tends to influence gestational loss (17.2% vs. 22.3%; Baruselli et al., 2010Baruselli PS, Ferreira RM, Sá MF Fo, Nasser LFT, Rodrigues CA, Bo GA. Bovine embryo transfer recipient synchronisation and management in tropical environments. Reprod Fertil Dev. 2010;22(1):67-74. http://doi.org/10.1071/RD09214. PMid:20003847.
http://doi.org/10.1071/RD09214...
). This corroborates the findings of Stewart et al. (2011)Stewart BM, Block J, Morelli P, Navarette AE, Amstalden M, Bonilla L, Hansen PJ, Bilby TR. Efficacy of embryo transfer in lactating dairy cows during summer using fresh or vitrified embryos produced in vitro with sex-sorted semen. J Dairy Sci. 2011;94(7):3437-45. http://doi.org/10.3168/jds.2010-4008. PMid:21700029.
http://doi.org/10.3168/jds.2010-4008...
and Demetrio et al. (2007)Demetrio DG, Santos RM, Demetrio CG, Vasconcelos JL. Factors affecting conception rates following artificial insemination or embryo transfer in lactating Holstein cows. J Dairy Sci. 2007;90(11):5073-82. http://doi.org/10.3168/jds.2007-0223. PMid:17954747.
http://doi.org/10.3168/jds.2007-0223...
,who observed greater gestational loss after the initial diagnosis in both in vitro and in vivo ET than in AI.
In a study conducted by Ealy, Seekford (2019)Ealy AD, Seekford ZK. Symposium review: predicting pregnancy loss in dairy cattle. J Dairy Sci. 2019;102(12):11798-804. http://doi.org/10.3168/jds.2019-17176. PMid:31587904.
http://doi.org/10.3168/jds.2019-17176...
on embryos produced in vitro, pregnancy rates ranged from 29.5% to 54.3% with an average of 40.1%. In contrast, for embryos produced in vivo, pregnancy rates were higher, ranging from 41.5% to 90% with an average of 64.1%. Furthermore, the pregnancy loss rates in IVP embryos range from 5% to 7% after 90 days of pregnancy. Surprisingly, only 27.1% of the cows that received IVP embryos were able to maintain pregnancy until term. Moreover, early embryonic loss (32 d) after fixed-time embryo transfer (FTET) in dairy cattle ranges from 53% (Diskin et al., 2006Diskin MG, Murphy JJ, Sreenan JM. Embryo survival in dairy cows managed under pastoral conditions. Anim Reprod Sci. 2006;96(3-4):297-311. http://doi.org/10.1016/j.anireprosci.2006.08.008.
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) to 58% (Pereira et al., 2016Pereira MHC, Wiltbank MC, Vasconcelos JLM. Expression of estrus improves fertility and decreases pregnancy losses in lactating dairy cows that receive artificial insemination or embryo transfer. J Dairy Sci. 2016;99(3):2237-47. http://doi.org/10.3168/jds.2015-9903. PMid:26723130.
http://doi.org/10.3168/jds.2015-9903...
).
Notably, bovine embryos are normally transferred to recipient females approximately seven days after estrus or early ovulation when the embryo has reached the blastocyst stage of development. Therefore, most biological, physiological, and technical causes of a female's failure to produce a blastocyst seven days after natural insemination or AI are avoided when a blastocyst-stage embryo is transferred to a female (Hansen, 2020Hansen PJ. The incompletely fulfilled promise of embryo transfer in cattle-why aren’t pregnancy rates greater and what can we do about it? J Anim Sci. 2020;98(11):skaa288. http://doi.org/10.1093/jas/skaa288. PMid:33141879.
http://doi.org/10.1093/jas/skaa288...
). Therefore, ET recipients are expected to have higher pregnancy success rates than inseminated females. However, except for heat stress or in cases where the female is a repeat breeder, in the absence of these infertility factors, the percentage pregnant cows after ET is generally equal to (or only slightly higher than) AI (Carter et al., 2008Carter F, Forde N, Duffy P, Wade M, Fair T, Crowe MA, Evans ACO, Kenny DA, Roche JF, Lonergan P. Effect of increasing progesterone concentration from Day 3 of pregnancy on subsequent embryo survival and development in beef heifers. Reprod Fertil Dev. 2008;20(3):368-75. http://doi.org/10.1071/RD07204. PMid:18402756.
http://doi.org/10.1071/RD07204...
; Sartori et al., 2002Sartori R, Sartor-Bergfelt R, Mertens SA, Guenther JN, Parrish JJ, Wiltbank MC. Fertilization and early embryonic development in heifers and lactating cows in summer and lactating and dry cows in winter. J Dairy Sci. 2002;85(11):2803-12. http://doi.org/10.3168/jds.S0022-0302(02)74367-1. PMid:12487447.
http://doi.org/10.3168/jds.S0022-0302(02...
; Wiltbank et al., 2016Wiltbank MC, Baez GM, Garcia-Guerra A, Toledo MZ, Monteiro PL, Melo LF, Ochoa JC, Santos JE, Sartori R. Pivotal periods for pregnancy loss during the first trimester of gestation in lactating dairy cows. Theriogenology. 2016;86(1):239-53. http://doi.org/10.1016/j.theriogenology.2016.04.037. PMid:27238438.
http://doi.org/10.1016/j.theriogenology....
- data compilated by Hansen 2020Hansen PJ. The incompletely fulfilled promise of embryo transfer in cattle-why aren’t pregnancy rates greater and what can we do about it? J Anim Sci. 2020;98(11):skaa288. http://doi.org/10.1093/jas/skaa288. PMid:33141879.
http://doi.org/10.1093/jas/skaa288...
).
In the following topics of this review, we addressed tools or alternatives to improve pregnancy success after ET, allowing the embryo's competence for survival and maternal capacity to support embryonic development. Among them are the production of a better embryo (with rigorous quality and stage classification) and improved uterine receptivity, taking into account the nutritional and health aspects, as well as the characteristics of the corpus luteum. In addition, we also examined the paternal effects on transferred embryos.
Strategies for minimize embryonic mortality
Embryo selection: different strategies to reduce losses
Observing the comparative results between embryonic losses derived from transferred embryos and conception rates by AI/TAI, we observed differences. Thus, efforts have been focused on reproductive biology research to determine the morphological, cellular, and molecular characteristics involved in the successful development of pregnancy. These efforts have advanced our understanding of the mechanisms for evaluating embryos transferred to recipients. Furthermore, these pregnancy losses typically occur in the first few weeks after ovulation or embryo transfer and are, on average, 40%–60% (Wiltbank et al., 2016Wiltbank MC, Baez GM, Garcia-Guerra A, Toledo MZ, Monteiro PL, Melo LF, Ochoa JC, Santos JE, Sartori R. Pivotal periods for pregnancy loss during the first trimester of gestation in lactating dairy cows. Theriogenology. 2016;86(1):239-53. http://doi.org/10.1016/j.theriogenology.2016.04.037. PMid:27238438.
http://doi.org/10.1016/j.theriogenology....
). Environmental factors can interfere with gametes and embryos quality; therefore, events occurring pre and post ovulation can affect the development of gametes, zygotes, and embryos (Denicol, Siqueira, 2023Denicol AC, Siqueira LGB. Maternal contributions to pregnancy success: from gamete quality to uterine environment. Anim Reprod. 2023;20(2):e20230085. http://doi.org/10.1590/1984-3143-ar2023-0085.
http://doi.org/10.1590/1984-3143-ar2023-...
). Compared with embryos produced in vivo, pregnancy rates of in vitro embryos are 10–40% lower than those of embryos produced in vivo (Ealy, Seekford, 2019Ealy AD, Seekford ZK. Symposium review: predicting pregnancy loss in dairy cattle. J Dairy Sci. 2019;102(12):11798-804. http://doi.org/10.3168/jds.2019-17176. PMid:31587904.
http://doi.org/10.3168/jds.2019-17176...
; Reese et al., 2020Reese ST, Franco GA, Poole RK, Hood R, Fernadez Montero L, Oliveira Filho RV, Cooke RF, Pohler KG. Pregnancy loss in beef cattle: A meta-analysis. Anim Reprod Sci. 2020;212:106251. http://doi.org/10.1016/j.anireprosci.2019.106251. PMid:31864492.
http://doi.org/10.1016/j.anireprosci.201...
).
In in vitro production, we evaluated the stages of development; however, oocyte competence occurred when the pre-ovulatory follicle and the oocyte itself needed to complete a series of cellular events (Blondin et al., 2002Blondin P, Bousquet D, Twagiramungu H, Barnes F, Sirard MA. Manipulation of follicular development to produce developmentally competent bovine oocytes. Biol Reprod. 2002;66(1):38-43. http://doi.org/10.1095/biolreprod66.1.38. PMid:11751261.
http://doi.org/10.1095/biolreprod66.1.38...
), such as the accumulation of organelles and maternal mRNA (Krisher, 2004Krisher RL. The effect of oocyte quality on development. J Anim Sci. 2004;82(E-Suppl):E14-23. https://doi.org/10.2527/2004.8213_supplE14x.
https://doi.org/10.2527/2004.8213_supplE...
), in addition to the resumption of meiosis (Franciosi et al., 2014Franciosi F, Coticchio G, Lodde V, Tessaro I, Modina SC, Fadini R, Dal Canto M, Renzini MM, Albertini DF, Luciano AM. Natriuretic peptide precursor C delays meiotic resumption and sustains gap junction-mediated communication in bovine cumulus-enclosed oocytes. Biol Reprod. 2014;91(3):61. http://doi.org/10.1095/biolreprod.114.118869. PMid:25078681.
http://doi.org/10.1095/biolreprod.114.11...
). Previous studies have shown that oocytes that mature in vivo are more competent in supporting embryonic development than those that mature in vitro (Rizos et al., 2002Rizos D, Ward F, Duffy P, Boland MP, Lonergan P. Consequences of bovine oocyte maturation, fertilization or early embryo development in vitro versus in vivo: implications for blastocyst yield and blastocyst quality. Mol Reprod Dev. 2002;61(2):234-48. http://doi.org/10.1002/mrd.1153. PMid:11803560.
http://doi.org/10.1002/mrd.1153...
). These differences may be due to differences in gene expression, transcription, and protein abundance in early embryos derived from these oocytes (Banliat et al., 2022Banliat C, Mahé C, Lavigne R, Com E, Pineau C, Labas V, Guyonnet B, Mermillod P, Saint-Dizier M. Dynamic Changes in the Proteome of Early Bovine Embryos Developed In Vivo. Front Cell Dev Biol. 2022;21(10):863700. http://doi.org/10.3389/fcell.2022.863700. PMid:35386205.
http://doi.org/10.3389/fcell.2022.863700...
).
Oocytes play an important role in initially supplying the embryo with mRNAs and organelles during maternal-to-zygotic transition. Therefore, the oocyte quality and changes in oogenesis and/or maturation can affect embryonic development. Furthermore, the presence of miRNAs is also important. MiRNAs are small non-coding RNAs that regulate gene expression after transcription. miRNAs are present in transcriptionally quiescent mature oocytes and preimplantation embryos and exhibit low levels of transcription prior to embryonic genome activation (Telford, Watson, Schultz, 1990Telford NA, Watson AJ, Schultz GA. Transition from maternal to embryonic control in early mammalian development: a comparison of several species. Mol Reprod Dev. 1990;26(1):90-100. http://doi.org/10.1002/mrd.1080260113. PMid:2189447.
http://doi.org/10.1002/mrd.1080260113...
; Misirlioglu et al., 2006Misirlioglu M, Page GP, Sagirkaya H, Kaya A, Parrish JJ, First NL, Memili E. Dynamics of global transcriptome in bovine matured oocytes and preimplantation embryos. Proc Natl Acad Sci USA. 2006;103(50):18905-10. http://doi.org/10.1073/pnas.0608247103. PMid:17142320.
http://doi.org/10.1073/pnas.0608247103...
).
In a recent study, 935 unique targets were identified in bovine embryos using 73 miRNAs on days three and five of development. Gene ontology for these targets showed enrichment for 54 terms, the most substantial being RNA polymerase II transcription, cell cycle, cell maturation, and most notably, stem cell differentiation (Paulson et al., 2022Paulson EE, Fishman EL, Schultz RM, Ross PJ. Embryonic microRNAs are essential for bovine preimplantation embryo development. Proc Natl Acad Sci USA. 2022;119(45):e2212942119. http://doi.org/10.1073/pnas.2212942119. PMid:36322738.
http://doi.org/10.1073/pnas.2212942119...
). These results indicate the essential role of miRNAs in bovine preimplantation and embryonic development.
In this context, pre-implantation embryos are extremely sensitive to the environment, resulting in changes in their development (Wooldridge et al., 2022Wooldridge LK, Keane JA, Rhoads ML, Ealy AD. Bioactive supplements influencing bovine in vitro embryo development. J Anim Sci. 2022;100(7):skac091. http://doi.org/10.1093/jas/skac091. PMid:35772761.
http://doi.org/10.1093/jas/skac091...
). Moreover, it is unremarkable that conditions during the preimplantation period can exert short-, medium-, and long-term effects on the embryo. This period of development involves a multitude of events that set the stage for future progression of pregnancy (Denicol, Siqueira, 2023Denicol AC, Siqueira LGB. Maternal contributions to pregnancy success: from gamete quality to uterine environment. Anim Reprod. 2023;20(2):e20230085. http://doi.org/10.1590/1984-3143-ar2023-0085.
http://doi.org/10.1590/1984-3143-ar2023-...
). Epigenetic markers, such as DNA methylation, are lost and reinserted during reprogramming for embryonic implantation under the influence of the environment (Burdge, Lillycrop, 2010Burdge GC, Lillycrop KA. Nutrition, epigenetics, and developmental plasticity: implications for understanding human disease. Annu Rev Nutr. 2010;30(1):315-39. http://doi.org/10.1146/annurev.nutr.012809.104751. PMid:20415585.
http://doi.org/10.1146/annurev.nutr.0128...
). The first cleavage division, degradation of maternal mRNA, minor and major embryonic genomic activation (Hamatani et al., 2004Hamatani T, Carter MG, Sharov AA, Ko MS. Dynamics of global gene expression changes during mouse preimplantation development. Dev Cell. 2004;6(1):117-31. http://doi.org/10.1016/S1534-5807(03)00373-3 PMid:14723852.
http://doi.org/10.1016/S1534-5807(03)003...
) and, differentiation of extraembryonic tissues (Grazul-Bilska et al., 2011Grazul-Bilska AT, Johnson ML, Borowicz PP, Minten M, Bilski JJ, Wroblewski R, Velimirovich M, Coupe LR, Redmer DA, Reynolds LP. Placental development during early pregnancy in sheep: cell proliferation, global methylation, and angiogenesis in the fetal placenta. Reproduction. 2011;141(4):529-40. http://doi.org/10.1530/REP-10-0505 PMid:21273368.
http://doi.org/10.1530/REP-10-0505...
), are among the distinct events that occur during preimplantation and can be affected by environmental signals. Finally, changes in the peri-ovulatory microenvironment, highlighting follicular fluid (Sohel et al., 2013Sohel MM, Hoelker M, Noferesti SS, Salilew-Wondim D, Tholen E, Looft C, Rings F, Uddin MJ, Spencer TE, Schellander K, Tesfaye D. Exosomal and Non-Exosomal Transport of Extra-Cellular microRNAs in Follicular Fluid: Implications for Bovine Oocyte Developmental Competence. PLoS One. 2013;8(11):e78505. http://doi.org/10.1371/journal.pone.0078505. PMid:24223816.
http://doi.org/10.1371/journal.pone.0078...
; Ávila et al., 2020) can have impacts during oocyte and embryonic development.
In bovine embryo transfer protocols at the blastocyst stage, embryos are normally transferred to recipient females approximately seven days after estrus or early ovulation. Once this embryo is transferred, all possibilities of the cow failing to produce blastocysts are covered, unlike in AI/TAI. However, the pregnancy rates are generally similar between ET and AI. Factors intrinsic to the recipient female are discussed in the following sections. Furthermore, factors related to embryo production stages and the means used, among other factors, can directly reflect the production rate and maintenance of embryo pregnancy in vitro. The success of maintaining a pregnancy after ET depends on the creation/selection of an embryo of extreme quality, improving the uterine receptivity of the recipient female, and optimizing the creation of new tools for the production and transfer of embryos (Hansen 2020Hansen PJ. The incompletely fulfilled promise of embryo transfer in cattle-why aren’t pregnancy rates greater and what can we do about it? J Anim Sci. 2020;98(11):skaa288. http://doi.org/10.1093/jas/skaa288. PMid:33141879.
http://doi.org/10.1093/jas/skaa288...
).
Embryos produced in vitro have a lower blastocyst yield per oocyte and lower embryo quality, contributing to greater sensitivity to cryopreservation, compared to those produced in vivo. At the beginning of IVM, the intrinsic quality of in vitro maturation is related to up to 60% of the failure to advance to the blastocyst stage. However, events that determine embryonic quality occur between the zygote and blastocyst stages (Lonergan et al., 2001Lonergan P, Rizos D, Ward F, Boland MP. Factors influencing oocyte and embryo quality in cattle. Reprod Nutr Dev. 2001;41(5):427-37. http://doi.org/10.1051/rnd:2001142. PMid:11993800.
http://doi.org/10.1051/rnd:2001142...
). Despite the advances in in vitro biotechniques, processing causes stress to oocytes and embryos, thereby affecting their development (Melo-Sterza and Poehland, 2021Melo-Sterza FA, Poehland R. Lipid Metabolism in Bovine Oocytes and Early Embryos under In Vivo, In Vitro, and Stress Conditions. Int J Mol Sci. 2021;22(7):3421. http://doi.org/10.3390/ijms22073421. PMid:33810351.
http://doi.org/10.3390/ijms22073421...
). Characteristics such as darker cytoplasm, a greater proportion of lipids from the TAG class (Abd El Razek et al., 2000Abd El Razek IM, Charpigny G, Kodja S, Marquant-Le Guienne B, Mermillod P, Guyader-Joly C, Humblot P. Differences in lipid composition between in vivo- and in vitro produced bovine embryos. Theriogenology. 2000;53:346.), vacuoles in trophoblastic cells, changes in intercellular connections (Fair et al., 2001Fair T, Lonergan P, Dinnyes A, Cottell D, Hyttel P, Ward FA, Boland MP. Ultrastructure of bovine blastocysts following cryopreservation: effect of method of embryo production on blastocyst quality. Mol Reprod Dev. 2001;58:186-95. http://doi.org/10.1002/1098-2795(200102)58:2<186::AID-MRD8>3.0.CO;2-N. PMid:11139231.
http://doi.org/10.1002/1098-2795(200102)...
) and greater fragility of the zona pellucida (Duby et al., 1997Duby RT, Hill JL, O’Callaghan D, Overstrom EW, Boland MP. Changes induced in the bovine zona pellucida by ovine and bovine oviducts. Theriogenology. 1997;47(1):332. http://doi.org/10.1016/S0093-691X(97)82459-4. ]
http://doi.org/10.1016/S0093-691X(97)824...
) have been reported as differences between in vitro and in vivo embryo production.
Physiologically, free radicals have pronounced effects on DNA, RNA, and protein synthesis; however, they can alter the cell membrane, increase the intracellular pH, and interfere with mitochondrial function (Dias, Pivato, Dode, 2017Dias LRO, Pivato I, Dode MAN. Change in energy metabolism of in vitro produced embryos: an alternative to make them more cryoresistant? Semina: Ciênc Agrár. 2017;38(4): 2237-2253. http://doi.org/10.5433/1679-0359.2017v38n4p2237.
http://doi.org/10.5433/1679-0359.2017v38...
). Embryos produced in vitro, mainly in high-oxygen tension systems (20%), suffer from an imbalance in the production and/or accumulation of ROS, which is characterized by oxidative stress. This imbalance can have harmful effects on embryonic development, including metabolic changes (Pawlak et al., 2024Pawlak P, Lipinska P, Sell-Kubiak E, Kajdasz A, Derebecka N, Warzych E. Energy metabolism disorders during in vitro maturation of bovine cumulus-oocyte complexes interfere with blastocyst quality and metabolism. Dev Biol. 2024;509:51-8. http://doi.org/10.1016/j.ydbio.2024.02.004. PMid:38342400.
http://doi.org/10.1016/j.ydbio.2024.02.0...
), reduction in ATP levels, lipid peroxidation, changes in protein synthesis, membrane permeability, and mitochondrial and endoplasmic reticulum function (Cagnone and Sirad, 2013; Yoon et al., 2014Yoon SB, Choi SA, Sim BW, Kim JS, Mun SE, Jeong PS, Yang HJ, Lee Y, Park YH, Song BS, Kim YH, Jeong KJ, Huh JW, Lee SR, Kim SU, Chang KT. Developmental Competence of Bovine Early Embryos Depends on the Coupled Response Between Oxidative and Endoplasmic Reticulum Stress. Biol Reprod. 2014;90(5):104. http://doi.org/10.1095/biolreprod.113.113480. PMid:24695629.
http://doi.org/10.1095/biolreprod.113.11...
).
However, from all the changes comparing IVP embryos to in vivo embryos, it is well established that better quality embryos result in higher pregnancy rates than lower quality embryos. Therefore, if embryos can be accurately evaluated and high-quality embryos can be selected for ET, the commercial value of the selected embryos would increase, with a subsequent decrease in the number of recipients required and an overall improvement in ET efficiency. Therefore, evaluating the embryo before transferring to the recipients is extremely important especially when this embryo is being used post freezing (Bó, Mapletoft, 2018Bó GA, Mapletoft RJ. Evaluation and classification of bovine embryos. Animal Reproduction (AR). 2018;10(3):344-8.).
To date, the most common way to determine embryonic quality has been through morphological assessments using stereomicroscopy (Hansen, 2020Hansen PJ. The incompletely fulfilled promise of embryo transfer in cattle-why aren’t pregnancy rates greater and what can we do about it? J Anim Sci. 2020;98(11):skaa288. http://doi.org/10.1093/jas/skaa288. PMid:33141879.
http://doi.org/10.1093/jas/skaa288...
). However, because embryonic quality is based on visual analysis, it varies between observers, has low reproducibility, and can be influenced by the observers (Rocha et al., 2017Rocha JC, Passalia FJ, Matos FD, Takahashi MB, Ciniciato DS, Maserati MP, Alves MF, de Almeida TG, Cardoso BL, Basso AC, Nogueira MFG. A Method Based on Artificial Intelligence To Fully Automatize The Evaluation of Bovine Blastocyst Images. Sci Rep. 2017;7(1):7659. http://doi.org/10.1038/s41598-017-08104-9. PMid:28794478.
http://doi.org/10.1038/s41598-017-08104-...
). Due to the subjectivity of this assessment, differences have already been observed in the ultrastructure (López-Damián et al., 2008López-Damián EP, Galina CS, Merchant H, Cedillo-Pelaez C, Asprón M. (2008). Assessment of Bos taurus embryos comparing stereoscopic microscopy and transmission electron microscopy. Journal of Cell and Animal Biology. 2008;2(3):072-078.) and the blastocyst transcriptome determined similarly using microscopy has already been observed (Driver et al., 2012Driver AM, Peñagaricano F, Huang W, Ahmad KR, Hackbart KS, Wiltbank MC, Khatib H. RNA-Seq analysis uncovers transcriptomic variations between morphologically similar in vivo-and in vitro-derived bovine blastocysts. BMC Genomics. 2012;13(118):1-9. http://doi.org/10.1186/1471-2164-13-118 PMid:22452724.
http://doi.org/10.1186/1471-2164-13-118...
). Thus, an ideal scenario would be a large-scale use to discover possible markers of embryonic quality with the aim of predicting post-transfer embryo survival and pregnancy outcomes. Consequently, a wide variety of methodologies, from optical methodologies to methodologies based on omics assessments, have been used to evaluate and analyze bovine embryos (Rabel et al., 2023Rabel RAC, Marchioretto PV, Bangert EA, Wilson K, Milner DJ, Wheeler MB. Pre-Implantation Bovine Embryo Evaluation-From Optics to Omics and Beyond. Animals (Basel). 2023;13(13):2102. http://doi.org/10.3390/ani13132102. PMid:37443900.
http://doi.org/10.3390/ani13132102...
).
Notably, the best-quality embryo must be selected with quality grade I (1: Excellent or Good. The embryos have a symmetrical and spherical mass with individual blastomeres that are uniform in size, color, and density, see in IETS, 2020IETS. Statistics of embryo collection and transfer in domestic farm animals. Embryo transfer News Letter, 39;2020.) and/or grade II quality for transfer to a recipient, and selection must be applied when this embryo goes through the cryopreservation process. Farin, Slenning, Britt (1999)Farin PW, Slenning BD, Britt JH. Estimates of pregnancy outcomes based on selection of bovine embryos produced in vivo or in vitro. Theriogenology. 1999;52(4):659-70. http://doi.org/10.1016/S0093-691X(99)00160-0. PMid:10734364.
http://doi.org/10.1016/S0093-691X(99)001...
concluded that embryos selected for better quality had higher pregnancy rates. Additionally, they highlighted the differences and subjectivity between the types of evaluators when selecting embryos (evaluated under a stereomicroscope). The difference in conception rates between the selected embryos with quality grades I and II in in vitro embryos of approximately 17% in heifers and 22% in lactating cows has already been observed, with the highest percentage being for quality grade I (Demétrio et al., 2020Demétrio DGB, Benedetti E, Demetrio CGB, Fonseca J, Oliveira M, Magalhaes A, Dos Santos RM. How can we improve embryo production and pregnancy outcomes of Holstein embryos produced in vitro? (12 years of practical results at a California dairy farm). Anim Reprod. 2020;17(3):e20200053. http://doi.org/10.1590/1984-3143-ar2020-0053. PMid:33029219.
http://doi.org/10.1590/1984-3143-ar2020-...
); while this difference in embryos transferred in vivo was 44.15% and 32.58%, for grade I and grade II, respectively, after 30 days of transfer into Simmental cows (Erdem et al., 2020Erdem H, Karasahin T, Alkan H, Dursun S, Satilmis F, Guler M. Effect of embryo quality and developmental stages on pregnancy rate during fresh embryo transfer in beef heifers. Trop Anim Health Prod. 2020;52(5):2541-7. http://doi.org/10.1007/s11250-020-02287-6 PMid:32445155.
http://doi.org/10.1007/s11250-020-02287-...
).
Additionally, there have been many questions about the best developmental stage for embryo transfer to the recipient. However, the vast majority of studies have shown that the developmental phase does not have much influence, but when evaluating embryonic quality, it is relevant at these stages. (Coleman et al., 1987Coleman DA, Dailey RA, Leffel RE, Baker RD. Estrous synchronization and establishment of pregnancy in bovine embryo transfer recipients. J Dairy Sci. 1987;70(4):858-66. http://doi.org/10.3168/jds.S0022-0302(87)80084-X. PMid:3473092.
http://doi.org/10.3168/jds.S0022-0302(87...
; Hasler, 2001Hasler JF. Factors affecting frozen and fresh embryo transfer pregnancy rates in cattle. Theriogenology. 2001;56(9):1401-15. http://doi.org/10.1016/S0093-691X(01)00643-4 PMid:11768807.
http://doi.org/10.1016/S0093-691X(01)006...
; Bényei et al., 2006Bényei B, Komlósi I, Pécsi A, Pollott G, Marcos CH, de Oliveira Campos A, Lemes MP. The effect of internal and external factors on bovine embryo transfer results in a tropical environment. Anim Reprod Sci. 2006;93(3–4):268-79. http://doi.org/10.1016/j.anireprosci.2005.07.012. PMid:16169166.
http://doi.org/10.1016/j.anireprosci.200...
; Ferraz et al., 2016Ferraz PA, Burnley C, Karanja J, Viera-Neto A, Santos JE, Chebel RC, Galvão KN. Factors affecting the success of a large embryo transfer program in Holstein cattle in a commercial herd in the southeast region of the United States. Theriogenology. 2016;86(7):1834-41. http://doi.org/10.1016/j.theriogenology.2016.05.032 PMid:27364084.
http://doi.org/10.1016/j.theriogenology....
; Erdem et al., 2020Erdem H, Karasahin T, Alkan H, Dursun S, Satilmis F, Guler M. Effect of embryo quality and developmental stages on pregnancy rate during fresh embryo transfer in beef heifers. Trop Anim Health Prod. 2020;52(5):2541-7. http://doi.org/10.1007/s11250-020-02287-6 PMid:32445155.
http://doi.org/10.1007/s11250-020-02287-...
). According, to Putney et al. (1988)Putney DJ, Thatcher WW, Drost M, Wright JM, DeLorenzo MA. Influence of environmental temperature on reproductive performance of bovine embryo donors and recipients in the southwest region of the United States. Theriogenology. 1988;30(5):905-22. http://doi.org/10.1016/S0093-691X(88)80053-0. PMid:16726533.
http://doi.org/10.1016/S0093-691X(88)800...
, the lowest pregnancy rate was achieved after the transfer of embryos at the morula stage; however,, there was an increase in the pregnancy rate according to embryonic development in the blastocyst phase, initial to expanded blastocysts.
Hasler et al. (1987)Hasler JF, McCauley AD, Lathrop WF, Foote RH. Effect of donor-embryo-recipient interactions on pregnancy rate in a large-scale bovine embryo transfer program. Theriogenology. 1987;27(1):139-68. http://doi.org/10.1016/0093-691X(87)90075-6.
http://doi.org/10.1016/0093-691X(87)9007...
determined that the highest pregnancy rate was achieved after transferring embryos at the early blastocyst and blastocyst stages and that both stages of development were associated with a higher pregnancy rate than the compact morula and expanded blastocyst. When the quality of the structures was evaluated, similar results were obtained: a higher pregnancy rate in the initial blastocyst and blastocyst. Furthermore, Park et al. (2023)Park J, Lee W, Saadelin IM, Bang S, Lee S, Yi J, Cho J. Improved pregnancy rate and sex ratio in fresh/frozen in vivo derived embryo transfer of Hanwoo (Bos taurus coreanae) cows. J Anim Sci Technol. 2023;65(4):779-91. http://doi.org/10.5187/jast.2023.e69 PMid:37970502.
http://doi.org/10.5187/jast.2023.e69...
showed that pregnancy rates in Hanwoo (Bos taurus coreanae) cows varied according to the stage of embryonic development of embryos transferred in vivo (67.86% vs. 63.49% for morula stage; 64.00% vs. 54.72% for early blastocysts; and 50.00% vs. 47.83% for blastocysts in fresh vs. frozen/thawed embryos, respectively). This difference between the results clarifies to technicians that particularities are still highly expressed in each situation/reality evaluated in the field. More studies and standardization of protocols for embryonic culture according to the different subspecies, categories, and conditions of animals are necessary.
In this context, to enhance the embryonic quality and development analysis, one of the most useful optical options with satisfactory results during bovine embryos evaluation is the Time-Lapse Monitoring (TLM) method; however, this method has not been used on a large-scale bovine production. Since embryonic development is a dynamic process, critical developmental phases may go unnoticed with traditional and unique morphological assessments (Rocha et al., 2017Rocha JC, Passalia FJ, Matos FD, Takahashi MB, Ciniciato DS, Maserati MP, Alves MF, de Almeida TG, Cardoso BL, Basso AC, Nogueira MFG. A Method Based on Artificial Intelligence To Fully Automatize The Evaluation of Bovine Blastocyst Images. Sci Rep. 2017;7(1):7659. http://doi.org/10.1038/s41598-017-08104-9. PMid:28794478.
http://doi.org/10.1038/s41598-017-08104-...
; Angel-Velez et al., 2023Angel-Velez D, De Coster T, Azari-Dolatabad N, Fernández-Montoro A, Benedetti C, Pavani K, Van Soom A, Pascottini OB, Smits K. Embryo morphokinetics derived from fresh and vitrified bovine oocytes predict blastocyst development and nuclear abnormalities. Sci Rep. 2023;13(1):4765. http://doi.org/10.1038/s41598-023-31268-6. PMid:36959320.
http://doi.org/10.1038/s41598-023-31268-...
; Magata, 2023Magata F. Time-lapse monitoring technologies for the selection of bovine in vitro fertilized embryos with high implantation potential. J Reprod Dev. 2023;69(2):57-64. http://doi.org/10.1262/jrd.2022-131. PMid:36775299.
http://doi.org/10.1262/jrd.2022-131...
). In addition, some studies have observed that morphokinetic indicators (MKIs), such as the timing of first cleavage, number of blastomeres at first cleavage, and number of blastomeres, could be used as markers to predict blastocyst quality and pregnancy outcomes (Sugimura, Akai, Imai, 2017Sugimura S, Akai T, Imai K. Selection of viable in vitro-fertilized bovine embryos using time-lapse monitoring in microwell culture dishes. J Reprod Dev. 2017;63(4):353-7. http://doi.org/10.1262/jrd.2017-041. PMid:28552887.
http://doi.org/10.1262/jrd.2017-041...
). Some researchers have even proposed that MKIs would be a superior solution to replace the IETS morphology-based classification systems (Rabel et al., 2023Rabel RAC, Marchioretto PV, Bangert EA, Wilson K, Milner DJ, Wheeler MB. Pre-Implantation Bovine Embryo Evaluation-From Optics to Omics and Beyond. Animals (Basel). 2023;13(13):2102. http://doi.org/10.3390/ani13132102. PMid:37443900.
http://doi.org/10.3390/ani13132102...
).
Since biomarkers are detected in-omics technologies, especially related to transcriptomics and metabolomics, presence of markers related to embryonic quality are also suspected (Saadi et al., 2014Saadi HAS, Vigneault C, Sargolzaei M, Gagné D, Fournier É, de Montera B, Chesnais J, Blondin P, Robert C. Impact of whole-genome amplification on the reliability of pre-transfer cattle embryo breeding value estimates. BMC Genomics. 2014;15(1):889. http://doi.org/10.1186/1471-2164-15-889. PMid:25305778.
http://doi.org/10.1186/1471-2164-15-889...
; Herrera, 2016Herrera C. Clinical Applications of Preimplantation Genetic Testing in Equine, Bovine, and Human Embryos. J Equine Vet Sci. 2016;41:29-34. http://doi.org/10.1016/j.jevs.2016.04.002.
http://doi.org/10.1016/j.jevs.2016.04.00...
; Mullaart, Wells, 2018Mullaart E, Wells D. Animal Biotechnology 2: Emerging Breeding Technologies. Springer: Berlin, Germany; 2018. Embryo biopsies for genomic selection; p. 81–94. http://doi.org/10.1007/978-3-319-92348-2_5.
http://doi.org/10.1007/978-3-319-92348-2...
). However, during field applications of these technologies, more questions are raised than provisional solutions. For example, if a transcriptomic or metabolomic assessment is used for evaluating embryos in the field, it would be possible to perform a biopsy and extract RNA from the entire embryo produced in each in vitro production cycle. Additionally, analysis of all the results in terms of time for transfer might be possible; however, this process is not feasible.
Another way of evaluating embryonic quality is through evaluating the culture medium. However, for reliable evaluation, embryos should be cultured individually–a method used in basic research for metabolomic evaluation. Therefore, although these tools are powerful and useful for understanding pre-implantation embryo development/physiology, their large-scale, field-based applicability is nearly impossible. Hence, traditional evaluation methods, such as selection based on the morphological aspects of stereomicroscopy, are still used. Furthermore, it is expected that innovations will occur to optimize and make new possibilities accessible for embryo evaluation and enhance conception rates.
Recipient selection
An inadequate uterine environment can lead to pregnancy loss even before the 7th day in an inseminated cow or after the transfer of a good embryo. Therefore, the selection of recipients is equally relevant to the selection of the donors and embryos to be transferred. In 1998, McMillan estimated that only approximately 40–50% of recipients were able to maintain the pregnancy. Other studies have shown that cows exhibit the same behavior after receiving several embryo transfers, with some resulting in pregnancy and others having difficulty getting pregnant or becoming empty (Geary et al., 2016Geary TW, Burns GW, Moraes JG, Moss JI, Denicol AC, Dobbs KB, Ortega MS, Hansen PJ, Wehrman ME, Neibergs H, O’Neil E, Behura S, Spencer TE. Identification of Beef Heifers with Superior Uterine Capacity for Pregnancy. Biol Reprod. 2016;95(2):47. http://doi.org/10.1095/biolreprod.116.141390. PMid:27417907.
http://doi.org/10.1095/biolreprod.116.14...
; Moraes et al., 2018Moraes JGN, Behura SK, Geary TW, Hansen PJ, Neibergs HL, Spencer TE. Uterine influences on conceptus development in fertility-classified animals. Proc Natl Acad Sci USA. 2018;115(8):E1749-E1758. http://doi.org/10.1073/pnas.1721191115 PMid:29432175.
http://doi.org/10.1073/pnas.1721191115...
). Further evidence of uterine receptivity problems as a cause of infertility was the finding that 32.4% of recipients, who received five embryos, were unable to become pregnant with any embryos (Martins et al., 2018Martins T, Sponchiado M, Ojeda-Rojas OA, Gonella-Diaza AM, Batista EOS, Cardoso BO, Rocha CC, Basso AC, Binelli M. Exacerbated conceptus signaling does not favor establishment of pregnancy in beef cattle. J Anim Sci Biotechnol. 2018;9(1):87. http://doi.org/10.1186/s40104-018-0302-9. PMid:30555692.
http://doi.org/10.1186/s40104-018-0302-9...
). Other factors directly interfering with pregnancy after the embryo transfer include low body condition scores (Wallace et al. 2015Wallace RM, Pohler KG, Smith MF, Green JA. Placental PAGs: gene origins, expression patterns, and use as markers of pregnancy. Reproduction. 2015;149(3):R115-26. http://doi.org/10.1530/REP-14-0485. PMid:25661256.
http://doi.org/10.1530/REP-14-0485...
), adequate health management (Aono et al., 2013Aono FH, Cooke RF, Alfieri AA, Vasconcelos JL. Effects of vaccination against reproductive diseases on reproductive performance of beef cows submitted to fixed-timed AI in Brazilian cow-calf operations. Theriogenology. 2013;79(2):242-8. http://doi.org/10.1016/j.theriogenology.2012.08.008. PMid:23174768.
http://doi.org/10.1016/j.theriogenology....
), lactation period of dairy cows (Hasler, 2001Hasler JF. Factors affecting frozen and fresh embryo transfer pregnancy rates in cattle. Theriogenology. 2001;56(9):1401-15. http://doi.org/10.1016/S0093-691X(01)00643-4 PMid:11768807.
http://doi.org/10.1016/S0093-691X(01)006...
; Ferraz et al., 2016Ferraz PA, Burnley C, Karanja J, Viera-Neto A, Santos JE, Chebel RC, Galvão KN. Factors affecting the success of a large embryo transfer program in Holstein cattle in a commercial herd in the southeast region of the United States. Theriogenology. 2016;86(7):1834-41. http://doi.org/10.1016/j.theriogenology.2016.05.032 PMid:27364084.
http://doi.org/10.1016/j.theriogenology....
), temperament, consequent management stress (Kasimanickam et al., 2018Kasimanickam RK, Hall JB, Estill CT, Kastelic JP, Joseph C, Abdel Aziz RL, Nak D. Flunixin meglumine improves pregnancy rate in embryo recipient beef cows with an excitable temperament. Theriogenology. 2018;107:70-7. http://doi.org/10.1016/j.theriogenology.2017.10.043 PMid:29132037.
http://doi.org/10.1016/j.theriogenology....
, 2019Kasimanickam R, Kasimanickam V, Gold J, Moore D, Kastelic JP, Pyrdek D, Ratzburg K. Injectable or transdermal flunixin meglumine improves pregnancy rates in embryo transfer recipient beef cows without altering returns to estrus. Theriogenology. 2019;140:8-17. http://doi.org/10.1016/j.theriogenology.2019.08.011 PMid:31421533.
http://doi.org/10.1016/j.theriogenology....
), and metabolic changes and diseases in the pre-and postpartum periods (Ferraz et al., 2016Ferraz PA, Burnley C, Karanja J, Viera-Neto A, Santos JE, Chebel RC, Galvão KN. Factors affecting the success of a large embryo transfer program in Holstein cattle in a commercial herd in the southeast region of the United States. Theriogenology. 2016;86(7):1834-41. http://doi.org/10.1016/j.theriogenology.2016.05.032 PMid:27364084.
http://doi.org/10.1016/j.theriogenology....
; Ribeiro et al., 2016Ribeiro ES, Gomes G, Greco LF, Cerri RLA, Vieira-Neto A, Monteiro PLJ Jr, Lima FS, Bisinotto RS, Thatcher WW, Santos JEP. Carryover effect of postpartum inflammatory diseases on developmental biology and fertility in lactating dairy cows. J Dairy Sci. 2016;99(3):2201-20. http://doi.org/10.3168/jds.2015-10337. PMid:26723113.
http://doi.org/10.3168/jds.2015-10337...
; Barbosa et al., 2018Barbosa LFSP, Oliveira WVC, Pereira MHC, Moreira MB, Vasconcelos CGC, Silper BF, Cerri RLA, Vasconcelos JLM. Somatic cell count and type of intramammary infection impacts fertility from in vitro produced embryo transfer. Theriogenology. 2018;108:291-6. http://doi.org/10.1016/j.theriogenology.2017.12.025. PMid:29277069.
http://doi.org/10.1016/j.theriogenology....
; Estrada-Cortés et al., 2019Estrada-Cortés E, Ortiz WG, Chebel RC, Jannaman EA, Moss JI, de Castro FC, Zolini AM, Staples CR, Hansen PJ. Embryo and cow factors affecting pregnancy per embryo transfer for multiple-service, lactating Holstein recipients. Transl Anim Sci. 2019;3(1):60-5. http://doi.org/10.1093/tas/txz009 PMid:32704778.
http://doi.org/10.1093/tas/txz009...
).
Sanity management
The presence of reproductive diseases in cattle herds is the main obstacle to the expansion of global livestock farming. Approximately 50% of embryonic deaths are linked to infectious diseases (Aono et al., 2013Aono FH, Cooke RF, Alfieri AA, Vasconcelos JL. Effects of vaccination against reproductive diseases on reproductive performance of beef cows submitted to fixed-timed AI in Brazilian cow-calf operations. Theriogenology. 2013;79(2):242-8. http://doi.org/10.1016/j.theriogenology.2012.08.008. PMid:23174768.
http://doi.org/10.1016/j.theriogenology....
). Questions have been raised regarding the potential risk of infection and the pathogenic effects of infectious diseases on preimplantation embryos since the advent of the commercialization of embryo transfer (Fray et al., 2000Fray MD, Mann GE, Clarke MC, Charleston B. Bovine viral diarrhoea virus: its effects on ovarian function in the cow. Vet Microbiol. 2000;77(1-2):185-94. http://doi.org/10.1016/S0378-1135(00)00275-3. PMid:11042412.
http://doi.org/10.1016/S0378-1135(00)002...
).
Bovine alpha-herpesvirus 1 (BoHV-1) and bovine viral diarrhea virus (BVDV), the etiological agents of infectious bovine rhinotracheitis (IBR) and bovine viral diarrhea (BVD), respectively, exert a notable influence on pregnancy loss in cattle (Aono et al., 2013Aono FH, Cooke RF, Alfieri AA, Vasconcelos JL. Effects of vaccination against reproductive diseases on reproductive performance of beef cows submitted to fixed-timed AI in Brazilian cow-calf operations. Theriogenology. 2013;79(2):242-8. http://doi.org/10.1016/j.theriogenology.2012.08.008. PMid:23174768.
http://doi.org/10.1016/j.theriogenology....
). BoHV-1 can directly affect ovarian functionality and embryonic quality, in addition to compromising oocyte viability (Bielanski et al., 2013Bielanski A, Algire J, Lalonde A, Garceac A. Embryos produced from fertilization with bovine viral diarrhea virus (BVDV)-infected semen and the risk of disease transmission to embryo transfer (ET) recipients and offspring. Theriogenology. 2013;80(5):451-5. http://doi.org/10.1016/j.theriogenology.2013.04.028. PMid:23768649.
http://doi.org/10.1016/j.theriogenology....
). Furthermore, infections that occur before conception result in viral invasion of maturing oocytes within the follicles (Rufino et al., 2006Rufino FA, Seneda MM, Alfieri AA. Impacto do herpesvírus bovino 1 e do vírus da diarréia viral bovina na transferência de embriões. Arch Vet Sci. 2006;11(1):78-84. http://doi.org/10.5380/avs.v11i1.5606.
http://doi.org/10.5380/avs.v11i1.5606...
). BVDV reaches reproductive tissues, interferes with follicular and embryonic development, and persists for weeks in the ovaries of infected females (Rahim-Tayefeh et al., 2023). Moreover, BVDV can infect embryos through donor females, reaching biological materials related to the technique (Bielanski et al., 2013Bielanski A, Algire J, Lalonde A, Garceac A. Embryos produced from fertilization with bovine viral diarrhea virus (BVDV)-infected semen and the risk of disease transmission to embryo transfer (ET) recipients and offspring. Theriogenology. 2013;80(5):451-5. http://doi.org/10.1016/j.theriogenology.2013.04.028. PMid:23768649.
http://doi.org/10.1016/j.theriogenology....
). Furthermore, infection with this virus is associated with ovarian hypoplasia in persistently infected cattle (Grooms et al., 1998Grooms DL, Brock KV, Pate JL, Day ML. Changes in ovarian follicles following acute infection with bovine viral diarrhea virus. Theriogenology. 1998;49(3):595-605. http://doi.org/10.1016/S0093-691X(98)00010-7. PMid:10732038.
http://doi.org/10.1016/S0093-691X(98)000...
), delayed follicular growth (González Altamiranda et al., 2020González Altamiranda EA, Arias ME, Kaiser GG, Mucci NC, Odeón AC, Felmer RN. Upregulation of interferon-alpha gene in bovine embryos produced in vitro in response to experimental infection with noncytophatic bovine-viral-diarrhea virus. Mol Biol Rep. 2020;47(12):9959-65. http://doi.org/10.1007/s11033-020-05958-7. PMid:33226564.
http://doi.org/10.1007/s11033-020-05958-...
), and reduced ovulation rates in response to treatments. superovulation (Kafi et al., 1997Kafi M, McGowan MR, Kirkland PD, Jillella D. The effect of bovine pestivirus infection on the superovulatory response of Friesian heifers. Theriogenology. 1997;48(6):985-96. http://doi.org/10.1016/S0093-691X(97)00325-7. PMid:16728188.
http://doi.org/10.1016/S0093-691X(97)003...
).
The interaction between BVDV biotypes and the oocyte zona pellucida affects the rate of early embryonic development during in vitro fertilization (Rahim-Tayefeh al., 2023). Briefly, BVDV can modify the expression of genes relevant to fundamental biological processes through the activation of signaling pathways, transcriptional regulation, and interference in the cellular microenvironment during persistent fetal infection (Hansen et al., 2010Hansen TR, Smirnova NP, Van Campen H, Shoemaker ML, Ptitsyn AA, Bielefeldt-Ohmann H. Maternal and fetal response to fetal persistent infection with bovine viral diarrhea virus. Am J Reprod Immunol. 2010;64(4):295-306. http://doi.org/10.1111/j.1600-0897.2010.00904.x. PMid:20678166.
http://doi.org/10.1111/j.1600-0897.2010....
).
Neosporosis, a disease caused by the parasite Neospora caninum that promotes infection in cattle, is one of the main causes of abortion and consequences for the embryo, birth of weak calves, neurological problems, and pregnancy loss in livestock (Rodríguez et al., 2022Rodríguez LEQ, Domínguez G, Alvarado Pinedo MF, Travería GE, Moré G, Campero LM, de la Sota RL, Madoz LV, Giuliodori MJ. Association of bovine viral diarrhea virus, bovine herpesvirus 1, and Neospora caninum with late embryonic losses in highly supplemented grazing dairy cows. Theriogenology. 2022;194:126-32. http://doi.org/10.1016/j.theriogenology.2022.10.002. PMid:36242875.
http://doi.org/10.1016/j.theriogenology....
). According to Pessoa et al. (2016)Pessoa GA, Martini AP, Trentin JM, Dalcin VC, Leonardi CEP, Vogel FSF, Sá MF Fo, Rubin MIB, Silva CAM. Impact of spontaneous Neospora caninum infection on pregnancy loss and subsequent pregnancy in grazing lactating dairy cows. Theriogenology. 2016;85(3):519-527. http://doi.org/10.1016/j.theriogenology.2015.09.034
http://doi.org/10.1016/j.theriogenology....
, cows seropositive for N. caninum have a higher incidence of pregnancy loss (35–270 days post-artificial insemination) than seronegative cows. Furthermore, N. caninum DNA was detected in 44.4% of the aborted fetuses from seropositive cows. In a study by De Souza et al. (2022)De Souza GG, Amatti LZ, Garcia LV, Costa LR, Minutti AF, Martins TA, Bogado ALG, Ignácio FS, de Almeida BFM, Garcia JL, de Barros LD. Neospora caninum infection and reproductive problems in dairy cows from Brazil: A case-control study. Vet Parasitol Reg Stud Reports. 2022;28:100683. http://doi.org/10.1016/j.vprsr.2021.100683. PMid:35115122.
http://doi.org/10.1016/j.vprsr.2021.1006...
, cows with a history of abortion were 2.3 times more likely to be seropositive for N. caninum. In addition, approximately 47.06% of females with a history of reproductive disorders tested positive for neosporosis, indicating an association between the infection and reproductive problems observed in this group of cows (De Souza et al., 2022De Souza GG, Amatti LZ, Garcia LV, Costa LR, Minutti AF, Martins TA, Bogado ALG, Ignácio FS, de Almeida BFM, Garcia JL, de Barros LD. Neospora caninum infection and reproductive problems in dairy cows from Brazil: A case-control study. Vet Parasitol Reg Stud Reports. 2022;28:100683. http://doi.org/10.1016/j.vprsr.2021.100683. PMid:35115122.
http://doi.org/10.1016/j.vprsr.2021.1006...
).
The management of infection caused by N. caninum requires the detection and separation of infected animals, adoption of appropriate breeding practices, vector control, and implementation of sanitary and biosecurity measures (Villa et al., 2022Villa L, Gazzonis AL, Allievi C, Zanzani SA, Mortarino M, Manfredi MT. Prevalence of Neospora caninum antibodies in fattening pigs and sows from intensive farms in northern Italy. Parasitol Res. 2022;121(3):1033-40. http://doi.org/10.1007/s00436-022-07457-z. PMid:35118513.
http://doi.org/10.1007/s00436-022-07457-...
). Moreover, it is crucial to adopt strict sanitary measures at all stages of the embryo transfer process. Techniques such as the polymerase chain reaction are effective tools for identifying the presence of viruses in embryos, uterine fluids, and lavage fluids (Rufino et al., 2006Rufino FA, Seneda MM, Alfieri AA. Impacto do herpesvírus bovino 1 e do vírus da diarréia viral bovina na transferência de embriões. Arch Vet Sci. 2006;11(1):78-84. http://doi.org/10.5380/avs.v11i1.5606.
http://doi.org/10.5380/avs.v11i1.5606...
). In addition, the exposure of bovine embryos to infectious agents during in vitro production may pose a potential risk of spreading infectious diseases (González Altamiranda et al., 2020González Altamiranda EA, Arias ME, Kaiser GG, Mucci NC, Odeón AC, Felmer RN. Upregulation of interferon-alpha gene in bovine embryos produced in vitro in response to experimental infection with noncytophatic bovine-viral-diarrhea virus. Mol Biol Rep. 2020;47(12):9959-65. http://doi.org/10.1007/s11033-020-05958-7. PMid:33226564.
http://doi.org/10.1007/s11033-020-05958-...
). Therefore, it is essential to monitor and prevent possible viral contamination in embryos to ensure the health and integrity of herds (Smirnova et al., 2012Smirnova NP, Webb BT, Bielefeldt-Ohmann H, Van Campen H, Antoniazzi AQ, Morarie SE, Hansen TR. Development of fetal and placental innate immune responses during establishment of persistent infection with bovine viral diarrhea virus. Virus Res. 2012;167(2):329-36. http://doi.org/10.1016/j.virusres.2012.05.018. PMid:22659490.
http://doi.org/10.1016/j.virusres.2012.0...
).
Nutritional management
Another important factor is body condition score (BCS). An adequate balance in carbohydrate intake is essential for maintaining pregnancy and preventing pregnancy loss. Metabolic factors such as the excessive formation of ketone bodies and increased blood urea nitrogen may be a threat to pregnancy (Szelényi et al., 2023Szelényi Z, Szenci O, Bodó S, Kovács L. Noninfectious causes of pregnancy loss at the late embryonic/early fetal stage in dairy cattle. Animals (Basel). 2023;13(21):3390. http://doi.org/10.3390/ani13213390. PMid:37958145.
http://doi.org/10.3390/ani13213390...
).
Although, Middleton, Minela, Pursley (2019)Middleton EL, Minela T, Pursley JR. The high-fertility cycle: how timely pregnancies in one lactation may lead to less body condition loss, fewer health issues, greater fertility, and reduced early pregnancy losses in the next lactation. J Dairy Sci. 2019;102(6):5577-87. http://doi.org/10.3168/jds.2018-15828. PMid:30904310.
http://doi.org/10.3168/jds.2018-15828...
and Santos et al. (2023)Santos GMG, Junior LB, Silva-Santos KC, Dias JHA, Dias IS, Seneda MM, Morotti F. Conception rate and pregnancy loss in fixed-time cattle embryo transfer programs are related to the luteal blood perfusion but not to the corpus luteum size. Theriogenology. 2023;210:251-5. http://doi.org/10.1016/j.theriogenology.2023.07.039. PMid:37549464.
http://doi.org/10.1016/j.theriogenology....
did not observe any interference in pregnancy loss rates according to BCS, Thangavelu et al. (2015)Thangavelu G, Gobikrushanth M, Colazo MG, Ambrose DJ. Pregnancy per Artificial Insemination and Pregnancy Loss in Lactating Dairy Cows of a Single Herd Following Timed Artificial Insemination or Insemination at Detected Estrus. Can J Anim Sci. 2015;95(3):383-8. http://doi.org/10.4141/cjas-2014-122.
http://doi.org/10.4141/cjas-2014-122...
showed a higher pregnancy loss rate in cows with a low BCS, reaching 9.1%, compared with females with a high BCS, which had a pregnancy loss rate of 1.9%. Furthermore, cows with a low BCS have a longer interval from calving to first estrus and are more frequently subjected to pregnancy loss (Spitzer et al., 1995Spitzer JC, Morrison DG, Wettemann RP, Faulkner LC. Reproductive responses and calf birth and weaning weights as affected by body condition at parturition and postpartum weight gain in primiparous beef cows. J Anim Sci. 1995;73(5):1251-7. http://doi.org/10.2527/1995.7351251x. PMid:7665355.
http://doi.org/10.2527/1995.7351251x...
). Female cattle with a BCS between 2–3 had a higher rate of pregnancy loss, corresponding to 14.91%, whereas cows with a BCS of 3 (1 to 5 points described by Lowman, Scott, Somerville, 1976Lowman BG, Scott NA, Somerville SH. Condition Scoring of Cattle. Edinburgh: East of Scotland College of Agriculture. Animal Production, Advisory and Development Department Edinburgh. Edinburgh School of Agriculture Bulletin, n. 6; 1976.) had a lower rate of pregnancy loss.
Moreover, the effect of BCS on the rate of late pregnancy loss was most substantial between days 43 and 53 after conception (Jones, Lamb, 2008Jones AL, Lamb GC. Nutrition, synchronization, and management of beef embryo transfer recipients. Theriogenology. 2008;69(1):107-15. http://doi.org/10.1016/j.theriogenology.2007.09.004 PMid:17964640.
http://doi.org/10.1016/j.theriogenology....
). Grimard et al. (2006)Grimard B, Freret S, Chevallier A, Pinto A, Ponsart C, Humblot P. Genetic and environmental factors influencing first service conception rate and late embryonic/foetal mortality in low fertility dairy herds. Anim Reprod Sci. 2006;91(1-2):31-44. http://doi.org/10.1016/j.anireprosci.2005.03.003. PMid:16310097.
http://doi.org/10.1016/j.anireprosci.200...
, reported that the incidence of late embryonic mortality was higher in high milk-producing cows and in cows with BCS ≥ 2.5 compared to cows with BCS < 2. Lima et al. (2022)Lima ACND, Pereira ETN, Almeida IDC, Xavier ED, Oliveira DCF, Almeida ACD. Reproductive disorders and reconception of beef cows subjected to timed artificial insemination. Cienc Anim Bras. 2022;23: e70384. http://doi.org/10.1590/1809-6891v22e-70384.
http://doi.org/10.1590/1809-6891v22e-703...
observed that cows that lost their body condition during days 28–56 of gestation had a higher rate (11.6%) of embryonic loss than cows that maintained (4.7%) or gained (5.7%) their body condition during this period. In addition, pregnancy loss rates have been observed to be relatively low, ranging from 3% to 5%, with primiparous females having a lower probability of pregnancy losses (ultrasound performed between 30 and 80 days) than multiparous cows (Zobel et al., 2011Zobel R, Tkalčić S, Pipal I, Buić V. Incidence and factors associated with early pregnancy losses in Simmental dairy cows. Anim Reprod Sci. 2011;127(3-4):121-5. http://doi.org/10.1016/j.anireprosci.2011.07.022. PMid:21906893.
http://doi.org/10.1016/j.anireprosci.201...
; Carvalho et al., 2014Carvalho PD, Souza AH, Amundson MC, Hackbart KS, Fuenzalida MJ, Herlihy MM, Ayres H, Dresch AR, Vieira LM, Guenther JN, Fricke PM, Shaver RD, Wiltbank MC. Relationships between Fertility and Postpartum Changes in Body Condition and Body Weight in Lactating Dairy Cows. J Dairy Sci. 2014;97(6):3666-83. http://doi.org/10.3168/jds.2013-7809. PMid:24731646.
http://doi.org/10.3168/jds.2013-7809...
).
Energy balance rather than physical condition or reproductive history is an accurate indicator for predicting pregnancy loss in primiparous and multiparous dairy cows, which have similar rates of pregnancy loss with normal and low BCS (Carvalho et al., 2014Carvalho PD, Souza AH, Amundson MC, Hackbart KS, Fuenzalida MJ, Herlihy MM, Ayres H, Dresch AR, Vieira LM, Guenther JN, Fricke PM, Shaver RD, Wiltbank MC. Relationships between Fertility and Postpartum Changes in Body Condition and Body Weight in Lactating Dairy Cows. J Dairy Sci. 2014;97(6):3666-83. http://doi.org/10.3168/jds.2013-7809. PMid:24731646.
http://doi.org/10.3168/jds.2013-7809...
). Dahl et al. (2020)Dahl MO, De Vries A, Galvão KN, Maunsell FP, Risco CA, Hernandez JA. Combined effect of mastitis and parity on pregnancy loss in lactating Holstein cows. Theriogenology. 2020;143:57-63. http://doi.org/10.1016/j.theriogenology.2019.12.002. PMid:31837631.
http://doi.org/10.1016/j.theriogenology....
noted a deterioration in embryonic quality in animals under unfavorable circumstances and in multiparous animals. Furthermore, females that deteriorated their body condition during early lactation showed significant changes in serum lipid levels and increased serum levels of non-esterified fatty acids, suggesting a molecular response in cumulus cells that may have an impact on embryo quality. and fertility (Ruebel et al., 2022Ruebel ML, Martins LR, Schall PZ, Pursley JR, Latham KE. Effects of early lactation body condition loss in dairy cows on serum lipid profiles and on oocyte and cumulus cell transcriptomes. J Dairy Sci. 2022;105(10):8470-84. http://doi.org/10.3168/jds.2022-21919. PMid:35940920.
http://doi.org/10.3168/jds.2022-21919...
).
Maintaining an adequate energy balance is especially important because it directly affects reproductive function, fertility, ovulation, embryo quality, and pregnancy maintenance. Feeding strategies that aim to meet specific nutritional needs at different stages of the reproductive cycle, such as the postpartum period, are essential to ensure reproductive health and minimize pregnancy loss rates (Jones; Lamb, 2008; Middleton, Minela, Pursley (2019)Middleton EL, Minela T, Pursley JR. The high-fertility cycle: how timely pregnancies in one lactation may lead to less body condition loss, fewer health issues, greater fertility, and reduced early pregnancy losses in the next lactation. J Dairy Sci. 2019;102(6):5577-87. http://doi.org/10.3168/jds.2018-15828. PMid:30904310.
http://doi.org/10.3168/jds.2018-15828...
.
Using the CL classification to select recipients
The success of ET depends on factors associated with the embryo and recipient cow, or even the interaction between these factors, the embryo-uterine environment, and the corpus luteum of the recipient. Recipient cows are one of the main factors (along with embryo selection discussed in the previous section) that determine successful pregnancy establishment after ET (Thomson et al., 2021Thomson SP, Holmes RJ, Landes PT, Allworth MB. Assessment and selection of the recipient cows’ corpus luteum at the time of embryo transfer, and its influence on conception rate. Aust Vet J. 2021;99(7):288-92. http://doi.org/10.1111/avj.13068. PMid:33913151.
http://doi.org/10.1111/avj.13068...
). Initially, in the development of the ET technique, the presence of the CL, which is an evidence of successful ovulation identified by transrectal palpation, was sufficient. The identification of the CL using B-mode ultrasound demonstrated a sensitivity of 86.2% and a specificity of 70.3% (Gómez-Seco et al., 2017Gómez-Seco C, Alegre B, Martínez-Pastor F, Prieto JG, González-Montaña JR, Alonso ME, Domínguez JC. Evolution of the corpus luteum volume determined ultrasonographically and its relation to the plasma progesterone concentration after artificial insemination in pregnant and non-pregnant dairy cows. Vet Res Commun. 2017;41(3):183-8. http://doi.org/10.1007/s11259-017-9685-x. PMid:28337578.
http://doi.org/10.1007/s11259-017-9685-x...
). Therefore, many commercial-scale transfer programs recommend only the identification of CL (Pontes et al., 2011Pontes JH, Melo Sterza FA, Basso AC, Ferreira CR, Sanches BV, Rubin KC, Seneda MM. Ovum pick up, in vitro embryo production, and pregnancy rates from a large-scale commercial program using Nelore cattle (Bos indicus) donors. Theriogenology. 2011;75(9):1640-6. http://doi.org/10.1016/j.theriogenology.2010.12.026. PMid:21334055.
http://doi.org/10.1016/j.theriogenology....
; Morotti et al., 2014Morotti F, Sanches BV, Pontes JH, Basso AC, Siqueira ER, Lisboa LA, Seneda MM. Pregnancy rate and birth rate of calves from a large-scale IVF program using reverse-sorted semen in Bos indicus, Bos indicus-taurus, and Bos taurus cattle. Theriogenology. 2014;81(5):696-701. http://doi.org/10.1016/j.theriogenology.2013.12.002 PMid:24412681.
http://doi.org/10.1016/j.theriogenology....
; Pellegrino et al., 2016Pellegrino CA, Morotti F, Untura RM, Pontes JH, Pellegrino MF, Campolina JP, Seneda MM, Barbosa FA, Henry M. Use of sexed sorted semen for fixed-time artificial insemination or fixed-time embryo transfer of in vitro-produced embryos in cattle. Theriogenology. 2016;86(3):888-93. http://doi.org/10.1016/j.theriogenology.2016.03.010 PMid:27068357.
http://doi.org/10.1016/j.theriogenology....
; Baruselli et al., 2018Baruselli PS, Ferreira RM, Colli MHA, Elliff FM, Sá Filho MF, Vieira L, Freitas BG. Timed artificial insemination: current challenges and recent advances in reproductive efficiency in beef and dairy herds in Brazil. Anim Reprod. 2018;14:558-71. http://doi.org/10.21451/1984-3143-AR999.
http://doi.org/10.21451/1984-3143-AR999...
; Lovarelli, Bacenetti, Guarino, 2020Lovarelli D, Bacenetti J, Guarino M. A review on dairy cattle farming: is precision livestock farming the compromise for an environmental, economic and social sustainable production? J Clean Prod. 2020;262:121409. http://doi.org/10.1016/j.jclepro.2020.121409.
http://doi.org/10.1016/j.jclepro.2020.12...
). However, it is known that evaluating the presence of CL in a recipient's ovary may be sufficient to assess the quality of the CL and consequently support pregnancy.
Although some studies have indicated that the CL size may be important for the maintenance of pregnancy (Gonella-Diaza et al., 2018Gonella-Diaza AM, Silveira Mesquita F, Lopes E, Ribeiro da Silva K, Cogliati B, De Francisco Strefezzi R, Binelli M. Sex steroids drive the remodeling of oviductal extracellular matrix in cattle. Biol Reprod. 2018;99(3):590-9. http://doi.org/10.1093/biolre/ioy083. PMid:29659700.
http://doi.org/10.1093/biolre/ioy083...
; Velho et al., 2022Velho GDS, Rovani MT, Ferreira R, Gasperin BG, Dalto AGC. Blood perfusion and diameter of bovine corpus luteum as predictors of luteal function in early pregnancy. Reprod Domest Anim. 2022;57(3):246-52. http://doi.org/10.1111/rda.14046. PMid:34773304.
http://doi.org/10.1111/rda.14046...
), others have not confirmed that the CL size is a mandatory aspect of pregnancy establishment (Pugliesi et al., 2019Pugliesi G, Dalmaso de Melo G, Silva JB, Carvalhêdo AS, Lopes E, Siqueira E Fo, Silva LA, Binelli M. Use of color-Doppler ultrasonography for selection of recipients in timed-embryo transfer programs in beef cattle. Theriogenology. 2019;135:73-9. http://doi.org/10.1016/j.theriogenology.2019.06.006. PMid:31203090.
http://doi.org/10.1016/j.theriogenology....
; Thomson et al., 2021Thomson SP, Holmes RJ, Landes PT, Allworth MB. Assessment and selection of the recipient cows’ corpus luteum at the time of embryo transfer, and its influence on conception rate. Aust Vet J. 2021;99(7):288-92. http://doi.org/10.1111/avj.13068. PMid:33913151.
http://doi.org/10.1111/avj.13068...
; Santos et al., 2023Santos GMG, Junior LB, Silva-Santos KC, Dias JHA, Dias IS, Seneda MM, Morotti F. Conception rate and pregnancy loss in fixed-time cattle embryo transfer programs are related to the luteal blood perfusion but not to the corpus luteum size. Theriogenology. 2023;210:251-5. http://doi.org/10.1016/j.theriogenology.2023.07.039. PMid:37549464.
http://doi.org/10.1016/j.theriogenology....
). Therefore, this issue requires further investigation, although there is a tendency to prioritize animals with CL.
Furthermore, the use of collor Doppler ultrasonography to evaluate blood perfusion in the CL has been intensively investigated. Several studies have demonstrated a direct relationship between the CL blood perfusion and pregnancy maintenance in FTET programs (Pinaffi et al., 2015Pinaffi FLV, Santos ES, Silva MG, Maturana Filho M, Madureira EH, Silva LA. Follicle and corpus luteum size and vascularity as predictors of fertility at the time of artificial insemination and embryo transfer in beef cattle. Pesq Vet Bras. 2015;35(5):470-6. http://doi.org/10.1590/S0100-736X2015000500015.
http://doi.org/10.1590/S0100-736X2015000...
; Pugliesi et al., 2018Pugliesi G, Melo GD, Ataíde GA Jr, Pellegrino CAG, Silva JB, Rocha CC, Motta IG, Vasconcelos JLM, Binelli M. Use of Doppler ultrasonography in embryo transfer programs: feasibility and field results. Anim Reprod. 2018;15(3):239-46. http://doi.org/10.21451/1984-3143-AR2018-0059. PMid:34178147.
http://doi.org/10.21451/1984-3143-AR2018...
; 2019Pugliesi G, Dalmaso de Melo G, Silva JB, Carvalhêdo AS, Lopes E, Siqueira E Fo, Silva LA, Binelli M. Use of color-Doppler ultrasonography for selection of recipients in timed-embryo transfer programs in beef cattle. Theriogenology. 2019;135:73-9. http://doi.org/10.1016/j.theriogenology.2019.06.006. PMid:31203090.
http://doi.org/10.1016/j.theriogenology....
; Santos et al., 2023Santos GMG, Junior LB, Silva-Santos KC, Dias JHA, Dias IS, Seneda MM, Morotti F. Conception rate and pregnancy loss in fixed-time cattle embryo transfer programs are related to the luteal blood perfusion but not to the corpus luteum size. Theriogenology. 2023;210:251-5. http://doi.org/10.1016/j.theriogenology.2023.07.039. PMid:37549464.
http://doi.org/10.1016/j.theriogenology....
; Rossignolo et al., 2023Rossignolo EAA, Silva NCD, Stolf RL, Cavalieri FLB, Colombo AHB, Andreazzi MA, Seneda MM, Morotti F. Evaluation of hCG as gonadotropic support to timed embryo transfer protocol in beef cattle. Theriogenology. 2023;195:24-30. http://doi.org/10.1016/j.theriogenology.2022.10.004. PMid:36274393.
http://doi.org/10.1016/j.theriogenology....
). Thus, cows and heifers with greater blood perfusion in the CL have higher serum concentrations of P4, and consequently, higher pregnancy rates (Gómez-Seco et al., 2017Gómez-Seco C, Alegre B, Martínez-Pastor F, Prieto JG, González-Montaña JR, Alonso ME, Domínguez JC. Evolution of the corpus luteum volume determined ultrasonographically and its relation to the plasma progesterone concentration after artificial insemination in pregnant and non-pregnant dairy cows. Vet Res Commun. 2017;41(3):183-8. http://doi.org/10.1007/s11259-017-9685-x. PMid:28337578.
http://doi.org/10.1007/s11259-017-9685-x...
; Fontes, Oosthuizen, 2022Fontes PLP, Oosthuizen N. Applied use of Doppler ultrasonography in bovine reproduction. Front. Anim. Sci. 2022;3:912854. http://doi.org/10.3389/fanim.2022.912854.
http://doi.org/10.3389/fanim.2022.912854...
).
A recent study evaluated a total of 1,700 Brangus recipients to determine whether area and luteal blood perfusion of corpus luteum (CL) may have any impact on the conception rate and the occurrence of pregnancy loss in a large-scale timed embryo transfer (TET) program (Santos et al., 2023Santos GMG, Junior LB, Silva-Santos KC, Dias JHA, Dias IS, Seneda MM, Morotti F. Conception rate and pregnancy loss in fixed-time cattle embryo transfer programs are related to the luteal blood perfusion but not to the corpus luteum size. Theriogenology. 2023;210:251-5. http://doi.org/10.1016/j.theriogenology.2023.07.039. PMid:37549464.
http://doi.org/10.1016/j.theriogenology....
). This study considered commercial IVP embryos in which all recipients with at least one CL received an embryo on the seventh day after ovulation. Each recipient was evaluated by B-mode ultrasound to determine the CL area (cm2) into small (< 3 cm2), medium (> 3 and < 4 cm2), and large (> 4 cm2), in addition to evaluation in color Doppler mode to classify luteal blood perfusion into low (vascularization < 40% of the CL), medium (vascularization > 45% and < 50%), and high score (vascularization > 50%). The results are expressed in Figure 1 and were interesting because it showed that the CL area/size did not affect (P > 0.1) the results of conception or pregnancy loss, but luteal blood flow determined an increase (P < 0.05) in the conception rate and a reduction (P < 0.05) in pregnancy loss. Therefore, strategically, this study showed that the use of Doppler ultrasound to evaluate recipients allows for a more accurate classification of the reproductive efficiency in embryo recipients. Positively impacting to increase the conception rate and reducing the occurrence of pregnancy loss, probably due to the better quality of the CL in the maintenance of pregnancy. All the results mentioned above demonstrate that CL assessment is necessary to predict possible pregnancy success. However, it is still necessary to use different techniques to predict good recipients of bovine embryos on a large scale, and possibly when different aspects are measured/addressed (CL size, CL perfusion, and serum progesterone dosage), the reliability seems to increase.
Effect of corpus luteum (CL) area/size (small < 3 cm2; medium > 3 and < 4 cm2; and large > 4 cm2) and blood flow score (low < 40% of CL; medium > 45% and < 50% of CL; and high > 55% of CL) on the conception rate in embryo recipients submitted to a timed embryo transfer (TET) program. Different lowercase (a-b), uppercase (A-B) or Greek letters (α-β) for the same variable indicate statistically significant differences (P < 0.05). There was no effect of CL area/size on conception rates at 30 and 90 days or on pregnancy loss.
Paternal contribution to gestational loss
Among the factors that contribute to gestational loss in cattle, paternal effects have been highlighted as important. This has been highlighted in studies involving dairy and beef livestock production (Franco et al., 2020Franco G, Reese S, Poole R, Rhinehart J, Thompson K, Cooke R, Pohler K. Sire contribution to pregnancy loss in different periods of embryonic and fetal development of beef cows. Theriogenology. 2020;154:84-91. http://doi.org/10.1016/j.theriogenology.2020.05.021. PMid:32535394.
http://doi.org/10.1016/j.theriogenology....
; Jena et al., 2021Jena SR, Nayak J, Kumar S, Kar S, Dixit A, Samanta L. Paternal contributors in recurrent pregnancy loss: cues from comparative proteome profiling of seminal extracellular vesicles. Mol Reprod Dev. 2021;88(1):96-112. http://doi.org/10.1002/mrd.23445. PMid:33345401.
http://doi.org/10.1002/mrd.23445...
; Pohler et al., 2021Pohler KG, Reese ST, Franco-Johannsen GA, de Melo GD, Oliveira R Fo, Poole RK. 265 Awardee Talk: maternal and paternal contributions to fertility. J Anim Sci. 2021;99(Suppl 3):137-8. http://doi.org/10.1093/jas/skab235.252.
http://doi.org/10.1093/jas/skab235.252...
). However, reproductive success is highly variable and is influenced by maternal and paternal factors. Maternal characteristics, including subspecies, parity, reproductive tract size, reproductive management strategies regarding estrus expression and detection, uterine environment, hormonal secretion, corpus luteum quality, and numerous other factors, can affect conception, pregnancy, and gestational loss (Pohler et al., 2021Pohler KG, Reese ST, Franco-Johannsen GA, de Melo GD, Oliveira R Fo, Poole RK. 265 Awardee Talk: maternal and paternal contributions to fertility. J Anim Sci. 2021;99(Suppl 3):137-8. http://doi.org/10.1093/jas/skab235.252.
http://doi.org/10.1093/jas/skab235.252...
). However, despite the numerous maternal factors involved in establishing pregnancy, the contribution of bulls to reproductive failure has rarely been investigated and is often completely neglected.
The establishment of pregnancy in cattle is a complex process that encompasses ovulation, fertilization, blastocyst formation, growth into an elongated conceptus, pregnancy recognition signaling, and the development of the embryo and placenta (Ortega et al., 2018Ortega MS, Moraes JGN, Patterson DJ, Smith MF, Behura SK, Poock S, Spencer TE. Influences of sire conception rate on pregnancy establishment in dairy cattle. Biol Reprod. 2018;99(6):1244-54. http://doi.org/10.1093/biolre/ioy141. PMid:29931362.
http://doi.org/10.1093/biolre/ioy141...
). Failure of any of these events can compromise embryonic development and gestational success. Paternal factors that determine gestational success act mainly in early pregnancy events (Starbuck et al., 2004Starbuck MJ, Dailey RA, Inskeep EK. Factors affecting retention of early pregnancy in dairy cattle. Anim Reprod Sci. 2004;84(1-2):27-39. http://doi.org/10.1016/j.anireprosci.2003.12.009. PMid:15302385.
http://doi.org/10.1016/j.anireprosci.200...
) and have a significant influence on placental and pregnancy losses (Pohler, Oliveira, 2024Pohler KG, Oliveira RV Fo. Impact of the sire on pregnancy loss. Vet Clin North Am Food Anim Pract. 2024;40(1):121-9. http://doi.org/10.1016/j.cvfa.2023.08.006. PMid:37884437.
http://doi.org/10.1016/j.cvfa.2023.08.00...
).
Chromosomal abnormalities caused by spermatogenesis-related disorders may be associated with recurrent embryonic mortality. A study evaluating chromosomal defects in the semen of a group of men with recurrent pregnancy loss, with (fertile group) or without (infertile group) eventual success in pregnancy through assisted reproduction, reported a higher incidence of aneuploidy in the sperm from the infertile group than in the fertile group of men (Cheung et al., 2019Cheung S, Parrella A, Rosenwaks Z, Palermo GD. Genetic and epigenetic profiling of the infertile male. PLoS One. 2019;14(3):e0214275. http://doi.org/10.1371/journal.pone.0214275. PMid:30897172.
http://doi.org/10.1371/journal.pone.0214...
). Furthermore, transcriptomic evaluation of fresh bovine semen identified transcripts that were substantially associated with fertilization and embryogenesis, with a greater abundance of THSD4 and PAG5 among the identified PAG proteins, both with strong associations with placental development (Selvaraju et al., 2017Selvaraju S, Parthipan S, Somashekar L, Kolte AP, Krishnan Binsila B, Arangasamy A, Ravindra JP. Occurrence and functional significance of the transcriptome in bovine (Bos taurus) spermatozoa. Sci Rep. 2017;7(1):42392. http://doi.org/10.1038/srep42392. PMid:28276431.
http://doi.org/10.1038/srep42392...
). Kropp et al. (2017)Kropp J, Carrillo JA, Namous H, Daniels A, Salih SM, Song J, Khatib H. Male fertility status is associated with DNA methylation signatures in sperm and transcriptomic profiles of bovine preimplantation embryos. BMC Genomics. 2017;18(1):280. http://doi.org/10.1186/s12864-017-3673-y. PMid:28381255.
http://doi.org/10.1186/s12864-017-3673-y...
analyzed embryos fertilized with either a high- or low-fertility Holstein bull, and RNA-sequencing analysis revealed that 98 genes were differentially expressed. A total of 65 genes were upregulated in high-fertility bull-derived embryos, and 33 genes were upregulated in low-fertility-derived embryos. Furthermore, evaluation of the epigenetic signature of spermatozoa between high- and low-fertility bulls revealed 76 differentially methylated regions.
Murine embryos with only a maternal genetic contribution presented an underdeveloped trophectoderm in the tissues of the conceptus, and embryos with only a paternal genetic contribution had a well-proliferated trophectoderm (Surani et al., 1987Surani MA, Barton SC, Norris ML. Influence of parental chromosomes on spatial specificity in androgenetic----parthenogenetic chimaeras in the mouse. Nature. 1987;326(6111):395-7. http://doi.org/10.1038/326395a0. PMid:3561479.
http://doi.org/10.1038/326395a0...
). A study conducted with parthenogenetic bovine embryos (embryos without a paternal genome; Pohler et al., 2021Pohler KG, Reese ST, Franco-Johannsen GA, de Melo GD, Oliveira R Fo, Poole RK. 265 Awardee Talk: maternal and paternal contributions to fertility. J Anim Sci. 2021;99(Suppl 3):137-8. http://doi.org/10.1093/jas/skab235.252.
http://doi.org/10.1093/jas/skab235.252...
) found that the trophectoderm was well-developed up to 30 days of gestation, but no site of embryo attachment to the endometrium was found. Furthermore, the secretion of pregnancy-associated glycoproteins (PAG) and interferon-stimulated genes was not found in the maternal circulation. These results suggest that paternal genetics are necessary for post-elongation attachment of the embryo to the endometrium.
To monitor the occurrence of gestational loss, in addition to ultrasound examination, the concentration of circulating PAG has been widely used, as it allows pregnancy diagnosis before 30 days of the conceptus, covering an earlier period and better reflecting the probability of pregnancy maintenance (Pohler et al., 2013Pohler KG, Geary TW, Johnson CL, Atkins JA, Jinks EM, Busch DC, Green JA, MacNeil MD, Smith MF. Circulating bovine pregnancy associated glycoproteins are associated with late embryonic/fetal survival but not ovulatory follicle size in suckled beef cows. J Anim Sci. 2013;91(9):4158-67. http://doi.org/10.2527/jas.2013-6348. PMid:23825331.
http://doi.org/10.2527/jas.2013-6348...
, 2016Pohler KG, Peres RFG, Green JA, Graff H, Martins T, Vasconcelos JLM, Smith MF. Use of bovine pregnancy-associated glycoproteins to predict late embryonic mortality in postpartum Nelore beef cows. Theriogenology. 2016;85(9):1652-9. http://doi.org/10.1016/j.theriogenology.2016.01.026. PMid:26928645.
http://doi.org/10.1016/j.theriogenology....
; Franco et al., 2018Franco GA, Peres RFG, Martins CFG, Reese ST, Vasconcelos JLM, Pohler KG. Sire contribution to pregnancy loss and pregnancy-associated glycoprotein production in Nelore cows. J Anim Sci. 2018;96(2):632-40. http://doi.org/10.1093/jas/sky015. PMid:29518245.
http://doi.org/10.1093/jas/sky015...
). Using PAG quantification and ultrasound at 30 and 60 d, the paternal effect (eight Angus bulls) was evaluated for pregnancy loss in 658 cows subjected to fixed-time insemination (TAI; Franco et al., 2020Franco G, Reese S, Poole R, Rhinehart J, Thompson K, Cooke R, Pohler K. Sire contribution to pregnancy loss in different periods of embryonic and fetal development of beef cows. Theriogenology. 2020;154:84-91. http://doi.org/10.1016/j.theriogenology.2020.05.021. PMid:32535394.
http://doi.org/10.1016/j.theriogenology....
). Overall, early embryonic death (between 24 and 30 days) was 5.54%, with values ranging from 1.8 to 11.7%, whereas late embryonic death was 6.7%, with values ranging from 2.3 to 12.6%. These results reinforce the importance of bulls’ contribution to the maintenance and establishment of pregnancy in cattle.
Heat stress negatively affects the reproductive performance of cattle and genetic differences in thermotolerance are known to occur. Generally, Bos indicus embryos are more thermotolerant than Bos taurus embryos (Hernandez-Ceron et al., 2004). This scenario is evident in females and is repeated in bulls. The use of Gir bulls (Bos indicus) to inseminate lactating Holstein cows resulted in a higher pregnancy rate and reduced pregnancy loss compared to Holstein bulls (Bos taurus; Pegorer et al., 2007Pegorer MF, Vasconcelos JL, Trinca LA, Hansen PJ, Barros CM. Influence of sire and sire breed (Gyr versus Holstein) on establishment of pregnancy and embryonic loss in lactating Holstein cows during summer heat stress. Theriogenology. 2007;67(4):692-7. http://doi.org/10.1016/j.theriogenology.2006.09.042. PMid:17118436.
http://doi.org/10.1016/j.theriogenology....
). Therefore, in addition to the other factors mentioned in this topic, the father's genetic group also stands out as another factor that can contribute to mitigating pregnancy loss, especially in herds that suffer the most from heat stress. Furthermore, it is believed that there is a link between the large variation in pregnancy rates among bulls when cows express estrus before TAI (Franco et al., 2018Franco GA, Peres RFG, Martins CFG, Reese ST, Vasconcelos JLM, Pohler KG. Sire contribution to pregnancy loss and pregnancy-associated glycoprotein production in Nelore cows. J Anim Sci. 2018;96(2):632-40. http://doi.org/10.1093/jas/sky015. PMid:29518245.
http://doi.org/10.1093/jas/sky015...
, 2020Franco G, Reese S, Poole R, Rhinehart J, Thompson K, Cooke R, Pohler K. Sire contribution to pregnancy loss in different periods of embryonic and fetal development of beef cows. Theriogenology. 2020;154:84-91. http://doi.org/10.1016/j.theriogenology.2020.05.021. PMid:32535394.
http://doi.org/10.1016/j.theriogenology....
) with the genetic/molecular characteristics of the sperm. Thus, there is a need for a better understanding of the molecular and genetic components of sperm, as well as the interaction between sperm and the female reproductive tract.
Finally, all the aforementioned selection criteria are extremely important for increasing conception rates on farms. Furthermore, several factors, such as seasonality and animal management, can affect the final results. In Chart 1, we summarize the strategies that can reduce EEM.
Possible solution strategies for early pregnancy loss considering the donor's embryonic classification, recipient selection, and paternal contribution.
Conclusion
Considering the economic impact of gestational loss on cattle farming, it is necessary to understand the mechanisms that lead to embryonic loss. Current knowledge refers to the consideration of basic aspects, such as nutrition, health, appropriate classification of embryos and recipients, and paternal effects, as the major points to minimize gestational losses. Despite the common situation of trying a single factor responsible for gestational failure, we highlight the importance of all conditions involved in cattle production, including animal welfare, to improve reproductive efficiency and minimize embryonic loss.
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Financial support: Supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq 405495/2023-4).
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How to cite: Seneda MM, Costa CB, Zangirolamo AF, Anjos MM, Paula GR, Morotti F. From the laboratory to the field: how to mitigate pregnancy losses in embryo transfer programs?. Anim Reprod. 2024;21(3):e20240032.
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Publication Dates
-
Publication in this collection
12 Aug 2024 -
Date of issue
2024
History
-
Received
15 Mar 2024 -
Accepted
29 Apr 2024