Pancreatic impairment and Igf2 hypermethylation induced by developmental exposure to bisphenol A can be counteracted by maternal folate supplementation.
Increasing evidence indicates that bisphenol A (BPA), a widely manufactured environmental pollutant, can induce changes in DNA methylation paatterns, which is a potential mechanism linking this environmental exposure to disease development. We investigated the influence of developmental exposure to BPA on pancreatic DNA methylation patterns and whether maternal folate supplementation can modify the epigenetic status and pancreatic impairment induced by BPA. Our results showed that maternal dietary folate supplementation in rats exposed to BPA counteracted the observed BPA-induced pancreatic impairments in the offspring, which included disrupted insulin secretion and glucose intolerance, and impaired morphology and ultrastructure of β cells. Moreover, these pancreatic dysfunctions were shown to be associated with low expression and DNA hypermethylation of insulin-like growth factor-2 (Igf2) in islets induced by exposure to BPA during the developmental period. Importantly, maternal dietary folate supplementation was demonstrated to negate this Igf2 DNA hypermethylation in the offspring, which was consistent with the upregulation of Igf2 expression. Overall, our results suggest that early developmental exposure to BPA alters the DNA methylation of Igf2, that these altered methylation patterns are associated with impaired β-cell function in the offspring and that these effects can be counteracted by maternal folate supplementation. Copyright © 2017 John Wiley & Sons, Ltd.
Department of Environmental Health, College of Public Health, Zhengzhou University, Zhengzhou, Henan, People's Republic of China.|Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China.
Zhenxing
Z
Mao
Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China.
Wei
W
Xia
Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China.
Wenqian
W
Huo
Department of Environmental Health Sciences, Yale School of Public Health, New Haven, CT, USA.
Tongzhang
T
Zheng
Department of Environmental Health Sciences, Yale School of Public Health, New Haven, CT, USA.
Bryan A
BA
Bassig
Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China.
Huailong
H
Chang
Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China.|Chinese Academy of Sciences, Shanghai Institutes for Biological Sciences in Institute of Biochemistry and Cell Biology, Shanghai, People's Republic of China.
Tian
T
Chen
Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China.
Feie
F
Li
Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China.
Yunxin
Y
Pan
Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China.
Yang
Y
Peng
Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China.
Yuanyuan
Y
Li
Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China.
Shunqing
S
Xu
D001559:Benzhydryl Compounds / Q000009:adverse effects*; D019175:DNA Methylation / Q000187:drug effects*; D019587:Dietary Supplements; D004785:Environmental Pollutants / Q000009:adverse effects; D005260:Female; D047109:Fetal Development / Q000187:drug effects; D005492:Folic Acid / Q000627:therapeutic use*; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000378:metabolism*; D008297:Male; D008431:Maternal-Fetal Exchange / Q000187:drug effects*; D010182:Pancreatic Diseases / Q000188:drug therapy* / Q000209:etiology*; D010636:Phenols / Q000009:adverse effects*; D011247:Pregnancy; D000098826:Bisphenol A Compounds
D001559:Benzhydryl Compounds; D004785:Environmental Pollutants; D005492:Folic Acid; D007335:Insulin-Like Growth Factor II; D010636:Phenols; C035170:IGF2 protein, human; C006780:bisphenol A; D000098826:Bisphenol A Compounds
DNA methylation; Igf2; bisphenol A; folate supplement; perinatal exposure