Backgrounds: To investigate the potential mechanism of hypospadias induced by DEHP in rats to reveal the preventative effect of TGF-β1 in hypospadias induced by DEHP via the reduction of EMT.
Methods: Time-mated Sprague-Dawley rats underwent cesarean section, and the penises of male pups were collected after exposure to corn oil or DEHP to establish a rat model of hypospadias and to further study the molecular mechanisms of hypospadias in vivo. In addition, the penises were cultured and treated with MEHP or MEHP+TGF-β1 in vitro. Subsequently, histomorphology and elements in TGF-β/Smad signaling pathway changes were evaluated using scanning electron microscopy, immunofluorescence, polymerase chain reaction, and western blot.
Results: The development of rat penis and urethral seam fusion were delayed after the treatment with DEHP in vivo or MEHP in vitro compared with the Control group. Moreover, TGF-β1, Smad2/Smad3, and the mesenchymal biomarkers, including α-SMA, N-cadherin, and Vimentin, were decreased. However, the epithelial biomarkers, including E-cadherin, ZO-1, β-catenin, and occludin, were increased. In addition, TGF-β1 could relieve all of the above changes.
Conclusion: Gestational DEHP exposure could lead to hypospadias by reducing urethral EMT. Moreover, TGF-β1 could prevent it by regenerating EMT through activating the TGF-β/Smad signal pathway.