Objective: The objective of this study is to analyze the effect of exogenous glial cell-derived neurotrophic factor (GDNF) in the development of the enteric nervous system (ENS) in the rectal end of fetal rats.
Materials and methods: Thirty pregnant Sprague-Dawley rats were categorized randomly into three groups: ethylene thiourea (ETU), ETU + GDNF, and control. On day 10 of gestation, ETU was injected via a gastric tube in the ETU group and ETU + GDNF group. On day 11 of gestation, GDNF was administered through the tail vein in the ETU + GDNF group. On day 20 of gestation, fetal rats were harvested by cesarean section. The prevalence of anorectal malformations (ARMs) in the fetal rats was observed. GDNF expression in the rectal end of fetal rats was detected by immunohistochemical and Western blotting analyses.
Results: The prevalence of ARMs in the ETU group and ETU + GDNF group was 51.4 and 52.5 %, respectively, but the difference between the two groups was not significant (P > 0.05). In the rectal end of fetal rats with an anus, GDNF expressions in the three groups were not significantly different (P > 0.05). In the rectal end of fetal rats without an anus: GDNF expression in the ETU + GDNF group was significantly higher than that in the ETU group (P = 0.036); GDNF expression in the rectal end of fetal rats without an anus from the ETU group and ETU + GDNF group was significantly lower than that of fetal rats with an anus (ETU group P = 0.001; ETU + GDNF group P = 0.028). There was a significant difference in the gray level ratio of GDNF and actin between the ETU group and ETU + GDNF group (P < 0.0001), and the expression in the ETU + GDNF group was significantly up-regulated.
Conclusion: GDNF could not totally prevent the occurrence of ETU-induced ARMs, but it up-regulated expression of the GDNF gene in the wall of the rectal end, thereby promoting the growth of a hypogenetic ENS.