Development and Reproduction (한국발생생물학회지:발생과생식)

The Korean Society of Developmental Biology (한국발생생물학회)
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Gestational Exposure to Bisphenol A Causes DNA Hypomethylation and the Upregulation of Progesterone Receptor Expression in the Uterus in Adult Female Offspring Rats

  • Seung Gee Lee (Department of Anatomy and Cell Biology, College of Medicine, Dong-A University) ;
  • Ji-Eun Park (Department of Anatomy and Cell Biology, College of Medicine, Dong-A University) ;
  • Yong-Pil Cheon (Division of Developmental Biology and Physiology, Department of Biotechnology, Sungshin University) ;
  • Jong-Min Kim (Department of Anatomy and Cell Biology, College of Medicine, Dong-A University)
  • Received : 2023.09.04
  • Accepted : 2023.11.14
  • Published : 2023.12.31
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Abstract

Exposure to environmental chemicals, including endocrine-disrupting chemicals, during the gestational period can have profound adverse effects on several organs in offspring. Bisphenol A (BPA) can infiltrate the human body through food and drinks, and its metabolites can cross both the placental and the blood-brain barriers. In this study, we investigate the effect of gestational exposure to BPA on epigenetic, biochemical, and histological modifications in the uterine tissues of F1 adult offspring rats. Pregnant rats were exposed to BPA from gestational day 8-15, and changes in global DNA methylation in uterine tissues obtained from adult offspring born to the exposed mothers were analyzed. Global DNA methylation analysis revealed that gestational exposure to BPA resulted in DNA hypomethylation in the uterus. Progesterone receptor (PR) protein expression in uterine tissues was monitored using western blot analysis, which revealed that the PR protein content was considerably higher in all BPA-exposed groups than in the control. Immunohistochemical examination for the PR revealed that intense PR-positive cells were more frequently observed in the BPA-exposed group than in the control group. To date, the evidence that the upregulation of PRs observed in the present study was caused by the non-methylation of specific PR promoter regions is lacking. Conclusively, these results indicate that exposure to BPA during gestation induces epigenetic alterations in the uteri of adult female offspring. We speculate that the global DNA hypomethylation and upregulation of the PR observed simultaneously in this study might be associated with the uterus.

Keywords

Acknowledgement

This study was supported by the National Research Foundation of Korea (NRF) Grant funded by the Korean government (MEST) (2009-0093191).

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