The expression of NGF and NGFR in distal rectum in fetal rats with anorectal malformations

Abstract

Objective To explore the role of GDNF in the development of enteric nervous system of the anorectal unit in fetal rats with malformations(ARM).Methods The ARM was induced by ethylenethiourea(ETU) in fetal rats.On day 20 of gestation,fetal rats were harvested by cesarean section for HE staining of the perineum in sagittal section.The protein and RNA expression levels of GDNF were studied by immunohistochemistry,Western blot and qRT-PCR.Results HE staining showed no opening at the end of the distal rectum in ARM fetuses,and thickened muscular layer of the terminal rectum which covered by hyperplastic squamous epithelial without intestinal gland.The number of submucosal and myenteric plexus also reduced significantly in ARM fetuses compared with controls (43.10 ± 8.60 vs 88.90 ± 10.65,P＜0.01).The expression of GDNF was mainly distributed in mucosal,submucosal plexus and myenteric plexus of the terminal rectum.The integral optical density (IOD)of GDNF was significantly lower in ARM fetuses than that of controls (238.32 ± 41.6750 vs 500.93 ± 90.10,P＜0.01).The protein and mRNA expression of GDNF of ARM fetuses were 0.43 ± 0.09; 72.00 ± 33.47,respectively,which were significantly lower than those of controls(0.61 ± 0.06,125.17 ± 66.28,P＜0.05).Conclusions The decreased expression of GDNF may play an important role in the maldevelopment of enteric nervous system in fetal rats with ARM. Key words: Glial cell line-derived neurotrophic factor; Enteric nervous system; Rectum