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Transgenerational effects of maternal bisphenol: a exposure on offspring metabolic health

Part of: DOHaD on International Women's Day 2020

Published online by Cambridge University Press:  26 October 2018

A. Bansal Open the ORCID record for A. Bansal [Opens in a new window] ,
C. Li ,
F. Xin ,
A. Duemler ,
W. Li ,
C. Rashid ,
M. S. Bartolomei  and
R. A. Simmons
A. Bansal
Affiliation:
Center for Research on Reproduction and Women’s Health, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA Center of Excellence in Environmental Toxicology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
C. Li
Affiliation:
Division of Endocrinology and Metabolism Department of Pediatrics, The Children’s Hospital of Philadelphia, Philadelphia, PA, USA
F. Xin
Affiliation:
Center of Excellence in Environmental Toxicology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA Epigenetics Institute, Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
A. Duemler
Affiliation:
Center for Research on Reproduction and Women’s Health, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA Eberly College of Science, Pennsylvania State University, University Park, PA, USA
W. Li
Affiliation:
Center for Research on Reproduction and Women’s Health, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA Center of Excellence in Environmental Toxicology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
C. Rashid
Affiliation:
Center for Research on Reproduction and Women’s Health, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA Center of Excellence in Environmental Toxicology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
M. S. Bartolomei
Affiliation:
Center for Research on Reproduction and Women’s Health, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA Center of Excellence in Environmental Toxicology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA Epigenetics Institute, Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
R. A. Simmons*
Affiliation:
Center for Research on Reproduction and Women’s Health, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA Center of Excellence in Environmental Toxicology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA Division of Neonatology, Department of Pediatrics, The Children’s Hospital of Philadelphia, Philadelphia, PA, USA
*
*Address for correspondence: Rebecca Simmons, MD, Center for Research on Reproduction and Women’s Health, Perelman School of Medicine, University of Pennsylvania, 1308 BRB II/III, Philadelphia, PA 19104, USA. E-mails: amitab@pennmedicine.upenn.edu or rsimmons@pennmedicine.upenn.edu
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Abstract

Exposure to the endocrine disruptor bisphenol A (BPA) is ubiquitous and associated with health abnormalities that persist in subsequent generations. However, transgenerational effects of BPA on metabolic health are not widely studied. In a maternal C57BL/6J mice (F0) exposure model using BPA doses that are relevant to human exposure levels (10 μg/kg/day, LowerB; 10 mg/kg/day, UpperB), we showed male- and dose-specific effects on pancreatic islets of the first (F1) and second generation (F2) offspring relative to controls (7% corn oil diet; control). In this study, we determined the transgenerational effects (F3) of BPA on metabolic health and pancreatic islets in our model. Adult F3 LowerB and UpperB male offspring had increased body weight relative to Controls, however glucose tolerance was similar in the three groups. F3 LowerB, but not UpperB, males had reduced β-cell mass and smaller islets which was associated with increased glucose-stimulated insulin secretion. Similar to F1 and F2 BPA male offspring, staining for markers of T-cells and macrophages (CD3 and F4/80) was increased in pancreas of F3 LowerB and UpperB male offspring, which was associated with changes in cytokine levels. In contrast to F3 BPA males, LowerB and UpperB female offspring had comparable body weight, glucose tolerance and insulin secretion as Controls. Thus, maternal BPA exposure resulted in fewer metabolic defects in F3 than F1 and F2 offspring, and these were sex- and dose-specific.

Keywords

β-cell massendocrine disruptorsinflammationinsulin secretionisletstransgenerational
Type
Original Article
Information
Journal of Developmental Origins of Health and Disease , Volume 10 , Issue 2 , April 2019 , pp. 164 - 175
Copyright
© Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2018. 

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Footnotes

The online version of this article has been updated since original publication. A notice detailing the changes has also been published at doi: 10.1017/S2040174418000934

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