The Expression of Shh, Ptch1, and Gli1 in the Developing Caudal Spinal Cord of Fetal Rats With Anorectal Malformations.

BACKGROUND:Postoperative incontinence and constipation still remain the major complications of anorectal malformations (ARMs), despite improvements in their treatment. One of the most important factors that affect postoperative anorectal function is malformations in the lumbosacral spinal cord. However, far too little attention has been paid to the underlying mechanism that produces these malformations. MATERIALS AND METHODS:The levels of sonic hedgehog (Shh), patched homolog 1 (Ptch1), and zinc finger-containing transcription factors 1 (Gli1) expression were investigated in the lumbosacral spinal cord in ethylenethiourea-exposed rat fetus with ARMs, and Shh, Ptch1, and Gli1 expression was confirmed with immunohistochemical staining, quantitative real-time polymerase chain reaction, and western blot analyses during lumbosacral spinal cord development both in the ARMs and normal rat embryos. RESULTS:Our results have shown that Shh, Ptch1, and Gli1 expression in the lumbosacral spinal cord of rat embryos with ARMs was decreased at both the messenger RNA and protein levels, when compared with their expression levels in normal tissues (P < 0.05). CONCLUSIONS:This study demonstrated that the expression of Shh, Ptch1, and Gli1 in lumbosacral spinal cord was remarkably reduced during late developmental stages in fetal rats with ARMs. These findings offered some important insights into the involvement of the Shh-Ptch1-Gli1 signaling pathway in the pathogenesis of lumbosacral spinal cord maldevelopment in rat fetus with ARMs, which leads to complications after procedures for ARMs.

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