Pubertal exposure to di-(2-ethylhexyl)-phthalate inhibits G9a-mediated histone methylation during spermatogenesis in mice

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• 作者：Chuan Liu ; Peng Qian ; Lingling Yang ; Lei Zhang ; Chunhai Chen…
• 关键词：Di ; (2 ; ethylhexyl) ; phthalate ; G9a ; Histone methylation ; Spermatogonial stem cell ; Meiosis
• 刊名：Archives of Toxicology
• 出版年：2016
• 出版时间：April 2016
• 年：2016
• 卷：90
• 期：4
• 页码：955-969
• 全文大小：12,164 KB
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• 作者单位：Chuan Liu (1)
  Peng Qian (1)
  Lingling Yang (1)
  Lei Zhang (1)
  Chunhai Chen (1)
  Mindi He (1)
  Yonghui Lu (1)
  Wei Feng (2)
  Min Li (1)
  Yanwen Zhang (1)
  Min Zhong (1)
  Zhengping Yu (1)
  Zhou Zhou (1)
  
  1. Department of Occupational Health, Third Military Medical University, Chongqing, 400038, People’s Republic of China
  2. Department of Occupational and Environmental Health, School of Public Health and Health Management, Chongqing Medical University, Chongqing, 400016, People’s Republic of China
  
• 刊物主题：Pharmacology/Toxicology; Occupational Medicine/Industrial Medicine; Environmental Health; Biomedicine general;
• 出版者：Springer Berlin Heidelberg
• ISSN：1432-0738

文摘

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.