Sharing of the same embryogenic pathway in anorectal malformations and anterior sacral myelomeningocele formation.

The objective of this study was to determine whether anorectal malformations (ARMs) and anterior sacral myelomeningocele share the same embryogenic pathway in a mouse model. Etretinate (Ro 10-9359) was administrated to C57BL/6 mice on gestation day 9 (E9). Sections of embryos and fetuses from E9.5 to E18 were observed by HE staining. Immunohistochemical staining with anti-NeuN and anti-GFAP was also done to determine cell origins of a presacral mass. In etretinate-treated embryos, neuroepithelial cells proliferated in the presacral region on E9.5. On E12, a canal appeared between the ectopic proliferated neuroepithelium and hindgut. On E13, anorectum abnormally kept a canal with the ventral urogenital tract through a fistula. On E13.5, a huge mass formed in the presacral region. On E18, 76.9% (30/39) of fetuses had ARMs, 100% (39/39) had a presacral mass (71.8% were huge) and 100% (39/39) had a sacral defect. The types of ARMs were mainly rectourethral or rectocloacal fistula. The presacral mass was anterior sacral myelomeningocele. We thus established the first mouse model of the Currarino triad, congenital caudal anomalies, including ARM, sacral abnormality and presacral mass. These disorders share the same embryogenic pathway. The teratogenic target of etretinate is the tail bud. Abnormal differentiation of the tail bud mesenchyme leads to defects of the tailgut and caudal neural tube. The abnormal mass blocks normal descent of the dorsal cloaca through the most posterior part of the cloacal plate.