Prenatal and early postnatal ethanol exposure induces hepatic transcriptional factors, gene expression transition and structural changes in the liver of offspring: A three month follow-up

Kashi, S and Kheradmand, F and Shirpoor, A.R and Pourjabali, M and Zeynali Moghaddam, SH and Rasmi, Y (2019) Prenatal and early postnatal ethanol exposure induces hepatic transcriptional factors, gene expression transition and structural changes in the liver of offspring: A three month follow-up. International Journal of Research in Applied and Basic Medical Sciences, 5 (1). pp. 9-17.

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Abstract

The aim of the present study was to investigate the effect of maternal pre- and early postnatal ethanol consumption on hepatic transcriptional factors, gene expression transition, liver enzymes alteration, as well as structural changes in the developing rat liver both on postnatal (PN) day 21 and 90. Materials & Methods: Pregnant Wistar rats received ethanol (4.5g/kg BW) once per day from Gestation Day (GD) 7 throughout lactation. The mRNA expression of hepatic Fatty Acid Translocase (FAT)/CD36, Protein Tyrosine Phosphatase 1B (PTP1B) and Hepatocyte Nuclear Factor 4 Alpha (HNF4A) gene expressions, as well as liver structural changes were measured in 21 and 90 dayold offspring of ethanol rats and were then compared to the control rats. Results: Ethanol exposed fetal livers showed a significant up-regulation in FAT / CD36, PTP1B and down-regulation in HNF4A gene expression, as well as an increase in the liver alanine aminotransferase (ALT) and aspartate aminotransferase (AST) of the offspring on PN 21 and PN 90 compared to the offspring in the control group. In addition, in the ethanol group, cholesterol levels showed a significant increase on PN 21 and PN 90, and triglyceride showed an increase on PN 90, compared to the control group. Histopathological changes, such as ballooning degeneration, feathery degeneration, spotty necrosis, cholestasis, and fibrosis were also observed in the liver of the offspring after 21 and 90 days from birth. Conclusion: In conclusion, results of the current study provide evidence that prenatal ethanol exposure influences liver lipid metabolism through hepatic transcriptional factors, gene expression transition and hepatic enzyme including ALT and AST changes

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