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论文类型：期刊论文

发表时间：2016-07-01

发表刊物：TOXICOLOGICAL SCIENCES

收录刊物：SCIE、Scopus

卷号：152

期号：1

页面范围：53-61

ISSN号：1096-6080

关键字：DEHP; Sertoli cells; differentiation; spermatogenesis

摘要：Mice may share similar mechanism with human underlying reproductive toxicity induced by di(2-ethylhexyl) phthalate (DEHP), which is not supposed to be associated with decreased testicular testosterone. Pregnant mice were exposed to DEHP by gavage, with the dosage regime beginning at human relevant exposure level. After in utero DEHP exposure, loss of Sertoli cells and germ cells were observed in the male pups at postnatal days 21. And SRY-related HMG box 9 (SOX9), Fibroblast growth factor-9 (FGF9), and Double-sex and Mab-3 related transcripttion factor 1 (DMRT1) proteins were significantly downregulated by DEHP at 2 mg/kg/d and above, suggesting the depression of Sertoli cell differentiation. The repression of Sox9 genes expression was supported by whole-mount in situ hybridization and real-time real-time-quantitative PCR. The expressions of Cyp11 alpha 1 and Star were not significantly affected by in utero DEHP exposure, indicating the absence of effects on testosterone biosynthesis. Furthermore, the testosterone-independent pathway regulating Sertoli cells differentiation was disturbed in fetus by DEHP at 2 mg/kg/d and above during the critical time window of sex determination, involving Gadd45g -> Gata4/Fog2 -> Sry -> Sox9 -> Fgf9. The results suggest that in utero DEHP exposure damaged Sertoli cells in the postnatal life of mice offspring via disturbance of the differentiation regulating pathway, potentially inducing declines in spermatogenesis.