Di(2-Ethylhexyl) Phthalate ExposureIn UteroDamages Sertoli Cell Differentiation Via Disturbance of Sex Determination Pathway in Fetal and Postnatal Mice

• DOI: 10.1093/toxsci/kfw063
• Publication Date: 2016-04-10T00:17:52Z
• Authors: Yongan Wang; Qing Yang; Wei Liu; Mingxi Yu; Zhou Zhang; Xiaoyu Cui
• Keywords: Anogenital distance; SOX9; FGF9; Sexual Differentiation; Testis determining factor

Mice may share similar mechanism with human underlying reproductive toxicity induced by di(2-ethylhexyl) phthalate (DEHP), which is not supposed to be associated decreased testicular testosterone. Pregnant mice were exposed DEHP gavage, the dosage regime beginning at relevant exposure level. After in utero exposure, loss of Sertoli cells and germ observed male pups postnatal days 21. And SRY-related HMG box 9 (SOX9), Fibroblast growth factor-9 (FGF9), Double-sex Mab-3 related transcripttion factor 1 (DMRT1) proteins significantly downregulated 2 mg/kg/d above, suggesting depression cell differentiation. The repression Sox9 genes expression was supported whole-mount situ hybridization real-time real-time-quantitative PCR. expressions Cyp11α1 Star affected indicating absence effects on testosterone biosynthesis. Furthermore, testosterone-independent pathway regulating differentiation disturbed fetus above during critical time window sex determination, involving Gadd45g → Gata4/Fog2 Sry Fgf9. results suggest that damaged life offspring via disturbance pathway, potentially inducing declines spermatogenesis.