Dynamic Effect of Di-2-(Ethylhexyl) Phthalate on Testicular Toxicity: Epigenetic Changes and Their Impact on Gene Expression

International Journal of Toxicology - Tập 29 Số 2 - Trang 193-200 - 2010
Shengde Wu1, Jing Zhu2, Yasha Li2, Tao Lin1, Liqiang Gan1, Xingang Yuan1, Mingdeng Xu1, Guanghui Wei1
1Department of Pediatric Urology Surgery, Children’s Hospital of Chongqing Medical University, Chongqing, China
2Department of Molecular Biology, Pediatric Research Institute, Children's Hospital of Chongqing Medical University, Chongqing, China

Tóm tắt

This study investigated epigenetic (specifically, DNA methylation) changes and their impact on gene expression in testes induced by maternal exposure to Di-2-(ethylhexyl) phthalate (DEHP) in mice. Testicular dysgenesis syndrome was induced in fetuses and pups by maternal exposure to DEHP at 500 mg/kg/d, and testes were excised for analysis on gestation day (GD) 19 and postnatal days (PNDs) 3, 21, 56, and 90. High-performance liquid chromatography (HPLC) was performed to analyze DNA methylation status, and expression levels of the DNA methyltransferases were examined by quantitative real-time polymerase chain reaction (qPCR). Testis-specific gene, insulin-like hormone 3 (Insl3), and testosterone production were also detected. DEHP significantly increased DNA methylation levels on GD 19 and PND 3 ( P < .05 and P < .05) but not on PNDs 21, 56, and 90. DEHP also significantly increased the expression of DNA methyltransferases. For DNA methyltransferase 1, the difference was not significant on PND 21, and DNA methyltransferase 3a and 3b returned to normal levels on PND 56. Fetal testes were a main target for DEHP as evidenced by a reduction in Insl3 expression and testosterone production. Effects of DEHP on Insl3 expression continued until PND 21. The DEHP-induced suppression of testosterone had not recovered on PND 56. Changes in DNA methylation may play an important role in abnormal testicular function caused by environmental factors such as maternal exposure to DEHP, which may be a mechanism of DEHP-mediated testicular toxicity.

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Thông tin xuất bản

International Journal of Toxicology

Tập 29 Số 2

193-200

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