Di(2-ethylhexyl) phthalate (DEHP) increases transforming growth factor-beta1 expression in fetal mouse genital tubercles.
Phthalates are known to elicit marked effects on the developing male reproductive tract as evidenced by hypospadias. Recently, transforming growth factor-beta1 (TGF-beta1) was postulated to play an essential role in the development of genital tubercles (GT), and TGF- beta1 was found to act as a phthalates-responsive gene. In this study, the effects of di(2-ethylhexyl) phthalate (DEHP) were examined on the expression of TGF-beta1 in fetal mice, as GT development is dependent upon this factor. Pregnant C57BL/6 mice were exposed to corn oil or DEHP (100, 200, or 500 mg/kg/d orally) from embryonic day 12 (ED12) to ED17. Data showed a significant inhibition of male fetal GT development following DEHP treatment. Hypospadic-like urethral orifice and abnormal urethra were evaluated macroscopically and by histology at ED19. By using reverse-transcription polymerase chain reaction (RT-PCR) and Western blot, the expression of TGF-beta1 was upregulated in DEHP-treated mice. These results suggest that hypospadias may be induced by DEHP exposure involving modification of TGF-beta1 levels.
Liu
Xing
X
Department of Urology, Chongqing Children's Hospital, Chongqing Medical University, Chongqing, China.
He
Da-Wei
DW
Zhang
De-Ying
DY
Lin
Tao
T
Wei
Guang-Hui
GH
D000818:Animals; D004051:Diethylhexyl Phthalate / Q000633:toxicity*; D005260:Female; D047109:Fetal Development / Q000187:drug effects*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D007021:Hypospadias / Q000209:etiology*; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects*; D051379:Mice; D011247:Pregnancy; D053773:Transforming Growth Factor beta1 / Q000187:drug effects*; D015854:Up-Regulation
D053773:Transforming Growth Factor beta1; D004051:Diethylhexyl Phthalate