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论文类型：期刊论文

发表时间：2015-10-02

发表刊物：TOXICOLOGY

收录刊物：SCIE、PubMed、Scopus

卷号：336

页面范围：10-16

ISSN号：0300-483X

关键字：DEHP; In utero exposure; Temporal expression; Sex determination

摘要：Animal researches and clinical studies have supported the relevance between phthalates exposure and testicular dysgenesis syndrome (TDS). These disorders may comprise common origin in fetal life, especially during sex determination and differentiation, where the mechanism remains unclear. The present study evaluated the disturbances in gene regulatory networks of sex determination in fetal mouse by in utero Di (2-ethylhexyl) phthalate (DEHP) exposure. Temporal expression of key sex determination genes were examined during the critical narrow time window, using whole-mount in situ hybridization and quantitative-PCR. DEHP exposure resulted in significant reduction in mRNA of Sry during sex determination from gestation day (GD) 11.0 to 11.5 in male fetal mice, and the increasing of Sly expression to threshold level on GD 11.5 was delayed. Meanwhile, Gadd45g and Gata4, the upstream genes of Sry, and downstream gene Sox9 were also significantly downregulated in expression. In fetal females, the expression of Wnt4 and beta-catenin were up-regulated by DEHP exposure. Taken together, the results suggest that the potential mechanism of gonadal development disorder by DEHP may origin from repression of important male sex determination signaling pathway, involving Gadd45g -> Gata4 -> Sry -> Sox9. The results would promote a better understanding of the association between phthalate esters (PAEs) exposure and the reductive disorder. (C) 2015 Elsevier Ireland Ltd. All rights reserved.