title: BPA-induced DNA hypermethylation of the master mitochondrial gene PGC-1α contributes to cardiomyopathy in male rats.
abstract: Implication of environmental endocrine disruptors, such as bisphenol A (BPA), on the development of cardiopathy has been poorly investigated. The aim of the study was to investigate the effects of long-term exposure to BPA at the reference dose on the myocardium of rats, and the underlying mechanisms. Male rats received corn oil or 50 μg/kg/day of BPA since delactation. At 24 and 48 weeks (wk), cardiac function and mitochondrial function were examined. The mRNA expression and the methylation status of PCG-1α, a major regulator of mitochondrial biogenesis in cardiac muscle, were also tested. At 48 wk, BPA-exposed rats displayed cardiomyopathy, characterized by myocardium hypertrophy, cardiomyocyte enlargement, and impairment of cardiac function. At 24 wk, significantly reduced ATP production, dissipated mitochondrial membrane potential (Ψm) and declined mitochondrial respiratory complex (MRC) activity in cardiomyocytes were observed in BPA-exposed rats compared with the control rats, indicating a decrease in mitochondrial function occurs before the development of cardiomyopathy. Additionally, BPA exposure decreased the expression of PGC-1α and induced hypermethylation of PGC-1 α in heart tissue in 24- and 48-week-old rats. The change in methylation of PGC-1α was observed more pronounced in BPA-exposed rats at 48 wk. Overall, long-term BPA exposure induces cardiomyopathy in male rats, and the underlying mechanism may involve the impairment of cardiac mitochondrial function and the disturbance of methylation of PGC-1α.
authors.affiliation: Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xia
authors.affiliation: Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Yang
authors.affiliation: Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Yingshuang
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Huailong
authors.initials: H
authors.lastname: Chang
authors.affiliation: Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Liu
authors.affiliation: Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Wenqian
authors.initials: W
authors.lastname: Huo
authors.affiliation: Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Xu
authors.affiliation: Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.affiliation: Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. Electronic address: liyuanyuan@hust.edu.cn.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. Electronic address: xust@hust.edu.cn.
authors.forename: Shunqing
authors.initials: S
authors.lastname: Xu
mesh_terms: D000818:Animals; D001559:Benzhydryl Compounds / Q000097:blood / Q000633:toxicity*; D001794:Blood Pressure; D009202:Cardiomyopathies / Q000235:genetics* / Q000378:metabolism; D019175:DNA Methylation / Q000187:drug effects*; D050259:Genes, Mitochondrial / Q000187:drug effects*; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D032342:Muscle Cells / Q000187:drug effects / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D010636:Phenols / Q000097:blood / Q000633:toxicity*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D010636:Phenols; D012333:RNA, Messenger; D014157:Transcription Factors; C501429:Ppargc1a protein, rat; C006780:bisphenol A; D000098826:Bisphenol A Compounds
keywords: Bisphenol A; Cardiomyopathy; DNA methylation; Mitochondrial dysfunction; PGC-1α