title: Pubertal exposure to di-(2-ethylhexyl)-phthalate inhibits G9a-mediated histone methylation during spermatogenesis in mice.
abstract: The increasing incidence of male reproductive impairments has been associated with di-(2-ethylhexyl)-phthalate (DEHP) exposure. However, mechanisms involved are lacking. We exposed 4-week-old male C57BL/6j mice to DEHP by gavage at 0, 125, 250 or 500 mg/kg body weight/day for 28 consecutive days. Our data showed that pubertal exposure to DEHP induces sperm count reduction as well as histological abnormalities in seminiferous epithelium and apoptosis of post-meiotic germ cells, and these effects are concomitant with reduction of testosterone levels and its steroidogenic gene expression. Moreover, the expressions of estrogen receptor ERβ and nuclear receptors Nr0b1, Nr0b2 are increased. The expression of Nr5a2 which is the inducer of steroidogenesis is significantly reduced. Furthermore, spermatogonial stem cell (SSC) self-renewal, differentiation and meiosis were significantly impaired, and the epigenetic regulator G9a-mediated histone methylation was decreased following DEHP exposure. Our results suggest that the DEHP-induced male reproductive impairments may depend on its estrogenic action on estrogen receptor and nuclear receptor, and involve inhibition of steroidogenesis, SSC self-renewal and meiosis, which may be attributed to the down-regulation of G9a-mediated histone methylation.
authors.affiliation: Department of Occupational Health, Third Military Medical University, Chongqing, 400038, People's Republic of China.
authors.forename: Chuan
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Occupational Health, Third Military Medical University, Chongqing, 400038, People's Republic of China.
authors.forename: Peng
authors.initials: P
authors.lastname: Qian
authors.affiliation: Department of Occupational Health, Third Military Medical University, Chongqing, 400038, People's Republic of China.
authors.forename: Lingling
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Occupational Health, Third Military Medical University, Chongqing, 400038, People's Republic of China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Occupational Health, Third Military Medical University, Chongqing, 400038, People's Republic of China.
authors.forename: Chunhai
authors.initials: C
authors.lastname: Chen
authors.affiliation: Department of Occupational Health, Third Military Medical University, Chongqing, 400038, People's Republic of China.
authors.forename: Mindi
authors.initials: M
authors.lastname: He
authors.affiliation: Department of Occupational Health, Third Military Medical University, Chongqing, 400038, People's Republic of China.
authors.forename: Yonghui
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Occupational and Environmental Health, School of Public Health and Health Management, Chongqing Medical University, Chongqing, 400016, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Feng
authors.affiliation: Department of Occupational Health, Third Military Medical University, Chongqing, 400038, People's Republic of China.
authors.forename: Min
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Occupational Health, Third Military Medical University, Chongqing, 400038, People's Republic of China.
authors.forename: Yanwen
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Occupational Health, Third Military Medical University, Chongqing, 400038, People's Republic of China.
authors.forename: Min
authors.initials: M
authors.lastname: Zhong
authors.affiliation: Department of Occupational Health, Third Military Medical University, Chongqing, 400038, People's Republic of China.
authors.forename: Zhengping
authors.initials: Z
authors.lastname: Yu
authors.affiliation: Department of Occupational Health, Third Military Medical University, Chongqing, 400038, People's Republic of China. lunazhou00@163.com.
authors.forename: Zhou
authors.initials: Z
authors.lastname: Zhou
mesh_terms: D000818:Animals; D004051:Diethylhexyl Phthalate / Q000633:toxicity*; D015536:Down-Regulation; D004781:Environmental Exposure / Q000009:adverse effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006657:Histones / Q000378:metabolism*; D008297:Male; D008540:Meiosis / Q000187:drug effects; D008745:Methylation / Q000187:drug effects*; D008810:Mice, Inbred C57BL; D012670:Seminiferous Epithelium / Q000187:drug effects / Q000473:pathology; D012741:Sexual Maturation / Q000187:drug effects; D013076:Sperm Count; D013091:Spermatogenesis / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D013094:Spermatozoa / Q000187:drug effects / Q000473:pathology; D013739:Testosterone / Q000378:metabolism
chemical_list: D006657:Histones; D013739:Testosterone; D004051:Diethylhexyl Phthalate
keywords: Di-(2-ethylhexyl)-phthalate; G9a; Histone methylation; Meiosis; Spermatogonial stem cell