Multigenerational effects of maternal Bisphenol A exposure on hepatic gene expression in mice.

Meer, T. van der (Tom) (2015) Multigenerational effects of maternal Bisphenol A exposure on hepatic gene expression in mice. thesis, Medicine.

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Abstract

Background: Bisphenol A (BPA), an endocrine disruptor found in polycarbonate plastic and epoxy resins, is associated with type 2 diabetes and obesity in humans and animals. We have previously demonstrated that BPA exposure in mothers (designated as the filial [F] 0) from 2 weeks prior to mating until weaning in C57BL/6 mice is associated with higher body fat and impaired glucose tolerance in male children (F1) and grandchildren (F2). The underlying mechanisms are unknown. In current study, we determined multigenerational effects of maternal BPA exposure on hepatic gene expression in mice. Methods: Livers were collected from 14-16 weeks old F1 and F2 offspring (n=2-5 per sex per group) of F0 mothers exposed to 10 μg/kg/day (LowerB), 10 mg/kg/day (UpperB) BPA and 7% corn oil (Control) diets. RNA isolation, RNA quantification, cDNA synthesis and Real-time PCR was performed. Fold change in mRNA expression was calculated with 95% confidence interval (p<0.05) using Pfaffl’s relative ratio. Results: F1 LowerB and UpperB males had reduced expression of irs2, akt2, pck2, slc2a2 and hk3 compared to Control male mice; LowerB also had reduced expression of g6pc, ppara, and srebf1. F1 LowerB and UpperB females had reduced expression of irs1, akt2, pck2, slc2a2, hk3 and srebf1 compared to Control female mice. F2 LowerB and UpperB males had reduced expression of pck2, slc2a2, and ppara compared to Control male mice; UpperB males also had reduced irs1, g6pc, akt2 and hk3. Conclusion: Early life lower and upper dose BPA exposure at representative human exposure levels leads to altered hepatic gene expression across two generations in mice. In males, reduced hepatic gene expression is associated with insulin resistance phenotypic data. In females, there may be post-transcriptional modifications, as the gene expression changes do not correlate with the earlier reported phenotypic outcomes. These findings need to be confirmed in a larger sample size.

Item Type:	Thesis (Thesis)
Supervisor name:	Faculty Supervisor: and Spronsen, Prof. dr. F.J. van
Supervisor name:	Second Supervisors: and Simmons, Rebecca A. MD; and Bansal, Amita PhD and Center for Research on Reproduction and Women's Health, Depa
Faculty:	Medical Sciences
Date Deposited:	25 Jun 2020 11:06
Last Modified:	25 Jun 2020 11:06
URI:	https://umcg.studenttheses.ub.rug.nl/id/eprint/2579

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