title: F0 maternal BPA exposure induced glucose intolerance of F2 generation through DNA methylation change in Gck.
abstract: BPA, a common environmental endocrine disruptor, has been reported to induce epigenetic changes and disrupt glucose homeostasis in F1 offspring through maternal exposure. However, no studies have examined whether maternal BPA exposure can exert multigenerational effects of glucose metabolic disorder on F2 generation through the altered epigenetic information. The aim of the current study was to investigate whether BPA exposure can disrupt glucose homeostasis in F2 offspring and the underlying epigenetic mechanism. In the present study, F0 pregnant dams were orally administered at a daily dose of 40μg/kg body weight during gestation and lactation. The F1 and F2 generations were obtained and not exposed to BPA anymore. The glucose and insulin tolerance tests were carried out to evaluate the glucose homeostasis level. The relative hormone level and the relative gene expression were also examined. F2 generation was found to exhibited glucose intolerance and insulin resistance in ipGTT and ipITT, as well as the downregulation of glucokinase (Gck) gene in liver. DNA methylation pattern of Gck promoter in the F2 generation of hepatic tissue and F1 generation of sperm was then performed. The Gck promoter in F2 hepatic tissue became completely methylated in the all CpG sites compared with five unmethylated sites in controls. In the F1 sperm, the global DNA methylation was decreased. However, there is only CpG site -314 was differently methylated between BPA and controls in sperm. In conclusion, F0 maternal BPA exposure during gestation and lactation can induce impaired glucose homeostasis in the F2 offspring through the transmission of sperm. The underlying epigenetic modifications in the sperm of F1 generation remain to be further elucidated.
authors.affiliation: Ministry of Education Key Laboratory of Environment and Health; School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Hangkong Road 13, Wuhan 430030, China.
authors.forename: Gengqi
authors.initials: G
authors.lastname: Li
authors.affiliation: Ministry of Education Key Laboratory of Environment and Health; School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Hangkong Road 13, Wuhan 430030, China.
authors.forename: Huailong
authors.initials: H
authors.lastname: Chang
authors.affiliation: Ministry of Education Key Laboratory of Environment and Health; School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Hangkong Road 13, Wuhan 430030, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xia
authors.affiliation: Ministry of Education Key Laboratory of Environment and Health; School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Hangkong Road 13, Wuhan 430030, China.
authors.forename: Zhenxing
authors.initials: Z
authors.lastname: Mao
authors.affiliation: Ministry of Education Key Laboratory of Environment and Health; School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Hangkong Road 13, Wuhan 430030, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Ministry of Education Key Laboratory of Environment and Health; School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Hangkong Road 13, Wuhan 430030, China. Electronic address: tjliyuanyuan@yahoo.com.cn.
authors.forename: Shunqing
authors.initials: S
authors.lastname: Xu
mesh_terms: D000818:Animals; D001559:Benzhydryl Compounds / Q000633:toxicity*; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D018899:CpG Islands; D019175:DNA Methylation; D052244:Endocrine Disruptors / Q000633:toxicity*; D044127:Epigenesis, Genetic; D005260:Female; D005865:Gestational Age; D005941:Glucokinase / Q000235:genetics* / Q000378:metabolism; D018149:Glucose Intolerance / Q000139:chemically induced* / Q000201:enzymology / Q000235:genetics*; D007333:Insulin Resistance; D007774:Lactation; D008297:Male; D018811:Maternal Exposure; D010636:Phenols / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011401:Promoter Regions, Genetic; D051381:Rats; D017207:Rats, Sprague-Dawley; D013094:Spermatozoa / Q000187:drug effects / Q000201:enzymology; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D015415:Biomarkers; D001786:Blood Glucose; D052244:Endocrine Disruptors; D005941:Glucokinase; D010636:Phenols; C006780:bisphenol A; D000098826:Bisphenol A Compounds
keywords: Bisphenol A; DNA methylation; F2 generation; Gck; Sperm