Di(2-ethylhexyl) phthalate (DEHP) increases transforming growth factor-beta1 expression in fetal mouse genital tubercles.
Кључне речи
Апстрактан
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.