Reduced Wnt3a expression correlates with poor development of the hindgut in rats with anorectal malformations

Abstract

Embryogenesis is orchestrated by the wingless-type MMTV integration site family (WNT) signaling pathways, including Wnt3a. This study was performed to investigate the expression of Wnt3a in the terminal hindgut in ethylenethiourea (ETU)-exposed rat embryos with anorectal malformations (ARMs) and its potential association between Wnt3a and the maldevelopment of the terminal hindgut in ARMs. ARM rat embryos were induced by ethylenethiourea on embryonic day 10 (E10). The expression levels of protein and mRNA of Wnt3a were confirmed using immunohistochemistry staining, Western blotting analyses, and quantitative real-time PCR (qRT-PCR) in normal rat and ARM embryos. Immunostaining revealed a variation in the expression of Wnt3a in the developing terminal hindgut of ARM embryos. The expression of Wnt3a in the terminal hindgut of ARM rat embryos decreased at both the mRNA level and protein level (P<0.05) compared with normal tissues. This study demonstrated that the expression of Wnt3a in the ARMs of ETU-exposed rat embryos was remarkably reduced, which indicated its potential role in the pathogenesis of the terminal hindgut maldevelopment in ARMs.

Keywords: Anorectal malformations; Development; Myenteric plexus; WNT.