Differential expression of the Wnt/β-catenin pathway in the genital tubercle (GT) of fetal male rat following maternal exposure to di-n-butyl phthalate (DBP)

Abstract

Di-n-butyl phthalate (DBP) is one of the most abundantly produced endocrine disruptors that leaches out from polyvinyl chloride plastics and can cause hypospadias in male rats during maternal exposure. The objective of this study was to first explore the roles of Wnt/β-catenin pathway in the fetal rat genital tubercle (GT) following in-utero exposure to DBP. Timed-pregnant rats were given DBP by gastric intubation at a dose of 750 mg/kg body weight (bw)/day from gestation day (GD) 14 to GD18 to establish a rat model of hypospadias. On GD19, genital tubercle down-regulation of β-catenin, Phospho-GSK-3β, and up-regulation of GSK-3β (glycogen synthase kinase-3β), NFκB in fetal male rats was observed by western blot analysis. β-catenin was located in the urethral plate epithelium (UPE). Immunochemistry showed that the relative expression of β-catenin decreased in the DBP-treated fetal rat GT compared to the normal control. These findings, for the first time, indicate that DBP may affect the development of GT by down-regulating the Wnt/β-catenin pathway in fetal male rats.

Keywords:

• β-catenin
• di-n-butyl phthalate
• genital tubercle
• hypospadias
• male rats

Acknowledgments

We would like to thank Professor J.H. Sha (Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China) for providing us with an excellent laboratory.

Declaration of Interest: The research was supported by grants from the National Natural Science Foundation of China (No. 30872596). The authors declare that there is no conflict of interest. The authors alone are responsible for the content and writing of the paper.