In utero repair of fetal rat myelomeningocele affects neuromuscular development in the bladder

Abstract

Fetal repair of myelomeningocele (MMC) has been proven to be beneficial for the central nervous system development; however, the effect of fetal MMC repair on bladder function remains controversial. The objective of the present study was to establish an early timepoint for in utero MMC repair using a rat model, and to investigate the changes in bladder development subsequent to that intervention. Sprague Dawley rats were divided into the MMC, MMC repair and control groups. MMC rat fetus models were created by treating pregnant rats with all-trans retinoic acid. The MMC defect was then repaired in utero at embryonic day 17 (E17) using a chitosan-gelatin membrane patch. Fetal rat bladders were removed at E19 and E21 in each group, as well as at stage E17 in the MMC and control groups. Differential expression of β-III-tubulin, α-smooth muscle actin (α-SMA), nerve growth factor (NGF) and acetylcholinesterase (AChE) mRNA, and β-III-tubulin and α-SMA protein in the bladder following fetal repair was measured and compared among the three groups. In addition, the expression of NGF mRNA was significantly elevated at E21 in the MMC group compared with that of the control group, however, the level decreased in the repair group at stage E21. The expression of α-SMA mRNA significantly increased at E19 and then decreased at E21 in the repair group compared with that of the MMC group; however, there were no significant changes in α-SMA protein following the repair. Furthermore, the repair enhanced β-III-tubulin mRNA expression at E19, but ameliorated the decrease of β-III-tubulin protein at E21. The expression of AChE mRNA increased in the MMC group at E19 and E21 compared with that of the control group, although it was not significantly altered following repair as compared with that of the MMC group. In conclusion, in the current study, abnormal neuromuscular development was observed in the MMC bladder, which enabled a certain degree of improvement in the in utero MMC repair.