Expression of the Shh/Bmp4 signaling pathway during the development of anorectal malformations in a male rat model of prenatal exposure to di(n-butyl) phthalate

Abstract

Sonic hedgehog (Shh)/bone morphogenetic protein 4 (Bmp4) is an androgen-regulated signaling pathway that has been shown to be crucial for embryonic development. This study was designed to investigate the expression of the Shh/Bmp4 signaling pathway during the development of anorectal malformations (ARMs) in male rats when prenatally exposed to di(n-butyl) phthalate (DBP). We found decreased serum testosterone concentration and reduced expression of the androgen receptor in the terminal rectum induced by DBP. In addition, significant decreases in mRNA and protein expression levels of Shh, GLI family zinc finger 2 (Gli2), GLI family zinc finger 3 (Gli3) and Bmp4 in the terminal rectum of male offspring induced by DBP were observed. Collectively, this study shows that the antiandrogenic effects of DBP disturb the androgen-related Shh/Bmp4 signaling pathway, which plays an important role in the occurrence of ARMs induced by DBP.