Impact of prenatal lipopolysaccharide exposure on the development of rats

The intrauterine environment is infl uenced by several factors, genetic or environmental, which are essential in understanding the pathophysiological mechanisms of some diseases. In this study, the aim was to investigate the impact of prenatal lipopolysaccharide exposure on the development of rats. Fifty pregnant rats received intraperitoneal administration of lipopolysaccharide (100 µg/kg), or saline at the same dose, on the 9.5th day of pregnancy. The offspring of these rats were analyzed for indicators of brain and somatic development and maturation of physical characteristics. Refl ex ontogenesis was also analyzed by vibrissae placement, negative geotaxis, palmar grasp, precipice aversion, decubitus recovery and acceleration reaction. Administration of lipopolysaccharide on the 9.5th gestational day caused delayed opening of the auditory pavilion, reduction in the length of the tail, body, cranial axes, and body weight. Thus, maternal infections can interfere in the intrauterine environment, impairing functional and structural aspects of the central nervous system, as well as the maturation of physical characteristics.

Key words
Developmental disorders; immune system; lipopolysaccharide; somatic development; sensory motor development

Authorship

MARINA G. SILVA

Programa de Pós-Graduação em Ciências da Saúde, Universidade do Sul de Santa Catarina, Laboratório de Neurociência Comportamental, Av. José Acácio Moreira, 787, Dehon, 88704-900 Tubarão, SC, BrazilUniversidade do Sul de Santa CatarinaBrazilTubarão, SC, BrazilPrograma de Pós-Graduação em Ciências da Saúde, Universidade do Sul de Santa Catarina, Laboratório de Neurociência Comportamental, Av. José Acácio Moreira, 787, Dehon, 88704-900 Tubarão, SC, Brazil

Programa de Pós-Graduação em Ciências da Saúde, Universidade do Sul de Santa Catarina, Laboratório de Neurobiologia de Processos Inflamatórios e Metabólicos, Av. José Acácio Moreira, 787, Dehon, 88704-900 Tubarão, SC, BrazilUniversidade do Sul de Santa CatarinaBrazilTubarão, SC, BrazilPrograma de Pós-Graduação em Ciências da Saúde, Universidade do Sul de Santa Catarina, Laboratório de Neurobiologia de Processos Inflamatórios e Metabólicos, Av. José Acácio Moreira, 787, Dehon, 88704-900 Tubarão, SC, Brazil

https://orcid.org/0000-0001-5354-7948

GUILHERME C. DAROS

https://orcid.org/0000-0001-7402-9154

GABRIELA M. SANTOS

https://orcid.org/0000-0002-1153-9349

ISABELLA P. ANGELINO

https://orcid.org/0000-0002-6661-0085

RAFAEL M. BITENCOURT

https://orcid.org/0000-0003-4694-3808

JUCÉLIA J. FORTUNATO

https://orcid.org/0000-0003-1780-0680

Correspondence to: Marina G. Silva E-mail: marina.goulartds@gmail.com

AUTHOR CONTRIBUTIONS

MGS and JJF conceptualized and designed the study. MGS, GCD, GMS and IPA conducted and evaluated the experiments. MGS and GCD analyzed and interpreted the data as well as wrote the first draft of the manuscript. RMB supervised the work and reviewed the manuscript. All authors have read and approved the final version of the manuscript.

SCIMAGO INSTITUTIONS RANKINGS

Figures

Figures (10)

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Figure 1
Effects of prenatal exposure to lipopolysaccharide (LPS), compared to the control group (SAL), on the development of rats: the anteroposterior axis of the skull (n=120). The evaluation was performed from the 1st to the 21st day of life. Data presented on average ± S.D. *p < 0.05.

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Figure 2
Effects of prenatal exposure to lipopolysaccharide (LPS), compared to the control group (SAL), on the development of rats: laterolateral axis of the skull (n=120). The evaluation was performed from the 1st to the 21st day of life. Data presented on average ± S.D. *p < 0.05.

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Figure 3
Effects of prenatal exposure to lipopolysaccharide (LPS), compared to the control group (SAL), on the development of rats: tail length (n=120). The evaluation was performed from the 1st to the 21st day of life. Data presented on average ± S.D. *p < 0.05.

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Figure 4
Effects of prenatal exposure to lipopolysaccharide (LPS), compared to the control group (SAL), on the development of rats: body length (n=120). The evaluation was performed from the 1st to the 21st day of life. Data presented on average ± S.D. *p < 0.05.

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Figure 5
Effects of prenatal exposure to lipopolysaccharide (LPS), compared to the control group (SAL), on the development of rats: body weight (n=120). The evaluation was performed from the 1st to the 21st day of life. Data presented on average ± S.D. *p < 0.05.

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Figure 6
Effects of prenatal exposure to lipopolysaccharide (LPS), compared to the control group (SAL), on the development of rats: somatic development (n=120). The evaluation was performed from the 1st to the 21st day of life. Data presented on average ± S.D. *p < 0.05. OAP = opening of the auditory pavilion; OAC = opening of the auditory conduit; OE = eye opening; II = eruption of lower incisors.

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Figure 7
Effects of prenatal exposure to lipopolysaccharide (LPS), compared to the control group (SAL), on the development of rats: reflex ontogenesis (n=20). The evaluation was performed from the 1st to the 21st day of life. Data presented on average ± S.D. *p < 0.05. DR = decubitus recovery; PA = precipice aversion; PG = palmar grasp; AR = acceleration reaction; NG = negative geotaxis.

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Figure 8
Effects of prenatal exposure to lipopolysaccharide (LPS), compared to the control group (SAL), on the development of rats: post mortem brain (n=17). The evaluation was performed on the 8th postnatal day. Data presented on average ± S.D. *p < 0.05. APEA = anterior-posterior encephalium axis; APBA = anterior-posterior brain axis; APCA = anterior-posterior cerebellum axis; LLBA = laterolateral axis of the brain; LLCA = laterolateral axis of the cerebellum; EW = encephalic weight; CW = cerebellum weight; DIAM = diameter; VOL = volume; CIRC = circumference.

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Figure 9
Effects of prenatal exposure to lipopolysaccharide (LPS), compared to the control group (SAL), on the development of rats: post mortem brain (n=23). The evaluation was performed on the 15th postnatal day. Data presented on average ± S.D. *p < 0.05. APEA = anterior-posterior encephalium axis; APBA = anterior-posterior brain axis; APCA = anterior-posterior cerebellum axis; LLBA = laterolateral axis of the brain; LLCA = laterolateral axis of the cerebellum; EW = encephalic weight; CW = cerebellum weight; DIAM = diameter; VOL = volume; CIRC = circumference.

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Figure 10
Effects of prenatal exposure to lipopolysaccharide (LPS), compared to the control group (SAL), on the development of rats: post mortem brain (n=24). The evaluation was performed on the 21st postnatal day. Data presented on average ± S.D. *p < 0.05. APEA = anterior-posterior encephalium axis; APBA = anterior-posterior brain axis; APCA = anterior-posterior cerebellum axis; LLBA = laterolateral axis of the brain; LLCA = laterolateral axis of the cerebellum; EW = encephalic weight; CW = cerebellum weight; DIAM = diameter; VOL = volume; CIRC = circumference.

Figure 1 Effects of prenatal exposure to lipopolysaccharide (LPS), compared to the control group (SAL), on the development of rats: the anteroposterior axis of the skull (n=120). The evaluation was performed from the 1st to the 21st day of life. Data presented on average ± S.D. *p < 0.05.

Figure 2 Effects of prenatal exposure to lipopolysaccharide (LPS), compared to the control group (SAL), on the development of rats: laterolateral axis of the skull (n=120). The evaluation was performed from the 1st to the 21st day of life. Data presented on average ± S.D. *p < 0.05.

Figure 3 Effects of prenatal exposure to lipopolysaccharide (LPS), compared to the control group (SAL), on the development of rats: tail length (n=120). The evaluation was performed from the 1st to the 21st day of life. Data presented on average ± S.D. *p < 0.05.

Figure 4 Effects of prenatal exposure to lipopolysaccharide (LPS), compared to the control group (SAL), on the development of rats: body length (n=120). The evaluation was performed from the 1st to the 21st day of life. Data presented on average ± S.D. *p < 0.05.

Figure 5 Effects of prenatal exposure to lipopolysaccharide (LPS), compared to the control group (SAL), on the development of rats: body weight (n=120). The evaluation was performed from the 1st to the 21st day of life. Data presented on average ± S.D. *p < 0.05.

Figure 6 Effects of prenatal exposure to lipopolysaccharide (LPS), compared to the control group (SAL), on the development of rats: somatic development (n=120). The evaluation was performed from the 1st to the 21st day of life. Data presented on average ± S.D. *p < 0.05. OAP = opening of the auditory pavilion; OAC = opening of the auditory conduit; OE = eye opening; II = eruption of lower incisors.

Figure 7 Effects of prenatal exposure to lipopolysaccharide (LPS), compared to the control group (SAL), on the development of rats: reflex ontogenesis (n=20). The evaluation was performed from the 1st to the 21st day of life. Data presented on average ± S.D. *p < 0.05. DR = decubitus recovery; PA = precipice aversion; PG = palmar grasp; AR = acceleration reaction; NG = negative geotaxis.

Figure 8 Effects of prenatal exposure to lipopolysaccharide (LPS), compared to the control group (SAL), on the development of rats: post mortem brain (n=17). The evaluation was performed on the 8th postnatal day. Data presented on average ± S.D. *p < 0.05. APEA = anterior-posterior encephalium axis; APBA = anterior-posterior brain axis; APCA = anterior-posterior cerebellum axis; LLBA = laterolateral axis of the brain; LLCA = laterolateral axis of the cerebellum; EW = encephalic weight; CW = cerebellum weight; DIAM = diameter; VOL = volume; CIRC = circumference.

Figure 9 Effects of prenatal exposure to lipopolysaccharide (LPS), compared to the control group (SAL), on the development of rats: post mortem brain (n=23). The evaluation was performed on the 15th postnatal day. Data presented on average ± S.D. *p < 0.05. APEA = anterior-posterior encephalium axis; APBA = anterior-posterior brain axis; APCA = anterior-posterior cerebellum axis; LLBA = laterolateral axis of the brain; LLCA = laterolateral axis of the cerebellum; EW = encephalic weight; CW = cerebellum weight; DIAM = diameter; VOL = volume; CIRC = circumference.

Figure 10 Effects of prenatal exposure to lipopolysaccharide (LPS), compared to the control group (SAL), on the development of rats: post mortem brain (n=24). The evaluation was performed on the 21st postnatal day. Data presented on average ± S.D. *p < 0.05. APEA = anterior-posterior encephalium axis; APBA = anterior-posterior brain axis; APCA = anterior-posterior cerebellum axis; LLBA = laterolateral axis of the brain; LLCA = laterolateral axis of the cerebellum; EW = encephalic weight; CW = cerebellum weight; DIAM = diameter; VOL = volume; CIRC = circumference.

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[1] Correspondence to: Marina G. Silva E-mail: marina.goulartds@gmail.com