The expressions of NGF and NTs receptors(TrkA and p75)in distal rectum of fetal rats with anorectal malformations

Abstract

Objective To study the expressions of nerve growth factor(NGF)and NTs receptors(TrkA and p75)in distal rectum of fetal rats with anorectal malformations(ARM).Methods Sixteen pregnant SD rats were divided into ARM group(n=10)and normal control group(n=6).Ethylenethiourea was administered to the pregnant rats by adding to drinking water to induce anorectal malformation in fetus between the 11th and 13th day of gestation.On the 20th day of gestation,fetuses were delivered by cesarean section.The fetuses were sectioned serially and sagittally,morphology of the distal rectum was studied.The expressions and distribution of NGF,TrkA and p75 in distal rectum and peritoneum of the fetuses were studied using immunohistochemical staining.Results The fetuses of the control group all survived after cesarean section and no abnormal rectal openings were found.The survival rate of the fetuses of ARM group was 80.7％.And ARM was found in 98.7％ of the fetuses.Other deformities were also noted including short-tailed deformity(25.1％),no tail deformity(74.8％),varus feet(6.4％),and spinal bifida(6.4％).On the sagittal section of peritoneum,there was no opening at the end of the distal rectum of the ARM fetuses,the end of the rectum had thickened muscular layer and covered by hyperplastic squamous epithelium without imestinal glands distribution.The numbers of submucosal and myenteric plexus also reduced significantly in ARM fetuses compared with controls(46.40±16.08 vs 96.33±18.5,P＜0.01).The NGF,TrkA,and p75-positive cells were mainly distributed in the terminal rectum mucosa and myenteric plexus.NGF protein was localized mainly in nucleus.TrkA protein was localized mainly in cytoplasm and p75 protein in nucleus and cytoplasm.The integral optical densities(IOD)of NGF,TrkA,and p75 of ARM fetuses were 17.97±74.95,33.15±11.13,113.01±36.47,respectively,which were significantly lower than those of controls(731.75±232.18,262.82±101.72,134.67±67.13,P＜0.05).Conclusions The expressions of NGF and NTs receptors are decreased in the rectum of rat fetuses with ARM,which suggests NGF and NTs receptors may play an important role in the pathogenesis of ARM. Key words: Anal canal,abnormalities; Rectum,abnormalities; Nerve growthfactor receptror