The effect of extrinsic neurotrophic factor during pregnancy on the enteric nervous system in the rectal end of mice with anorectal malformations

Abstract

Objective To study the influence of the extrinsic glial cell line-derived neurotrophic factor (GDNF) on the enteric nervous system (ENS) upgrowth in the rectal end of fetal mice.Methods SD pregnant mice were randomly divided into 3 groups,namely ETU group,ETU + GDNF group and control group.On the tenth day of pregnancy,ETU group and ETU+ GDNF group were given 1％ ETU via gavage.On the eleventh day of pregnancy,ETU+ GDNF group was injected with 20 μgGDNF by caudal vein.On the twentieth day of pregnancy,pregnant mice underwent the cesarian sections.The incidence of ARMs and the expression of GDNF in the rectal end of the fetal mice were detected by immunohistochemistry and western-blotting.Results 1.The incidence of ARMs in ETU group and ETU + GDNF group was 51.4％ and 52.5％,respectively,and there was no statistical difference (P＞0.05).2.Results of GDNF:① In the rectal end of the fetal mice with normal anus,there were no significant differences in the expression of GDNF among the three groups [ETU group:(0.051 ± 0.004) ％ ; ETU + GDNF group:(0.058 ± 0.004) ％ ; control group:(0.057 ± 0.004) ％,P ＞0.05].② In the rectal end of the fetal mice with ARMs,the expression of GDNF in ETU+ GDNF group was higher than that in ETU group [(0.043 ± 0.005) ％ vs (0.028 ± 0.005) ％,P =0.0366] ;and the expression in the rectal end of the fetal mice with ARMs in ETU group and ETU + GDNF group was lower than that in the rectal end of fetal mice with normal anus,respectively[ETU group:(0.028 ± 0.005) ％ vs (0.051 ± 0.004) ％,P =0.001 2; ETU + GDNF group:(0.043 ± 0.005) ％ vs (0.058 ± 0.004) ％,P =0.028 5].The expression of GDNF by western-blotting in ETU + GDNF group was significantly higher than that in ETU group (0.019 ± 0.003 vs 0.048 ± 0.003,P＜0.000 1).Conclusions Extrinsic neurotrophic factor (GDNF) may not block the teratogenesis of ARMs induced by ethylenethiourea,but may advance the expression of GDNF gene in the rectal end and promote the development of the dysplastic ENS. Key words: Anus, abnormalities; Rectum, abnormalities; Enteric nervous system; Glial cell line-derived neurotrophic factor