BACKGROUND/ PURPOSE: Recent biological studies have elucidated the molecular mechanism of muscle development, in which various regulatory molecules play key roles during embryogenesis. To determine possible myogenic abnormalities in anorectal malformations (ARM), the authors investigated the pelvic muscle development in murine embryos affected with ARM. METHODS: ARM embryos were induced by all-trans retinoic acid (ATRA) on the ninth gestational day (E9.0). Embryonal specimens were obtained from the uteri between E10.5 and E16.0, and the frozen sections were prepared for immunohistochemistry using antibodies specific for MyoD, myogenin, and PGP9.5 molecules. RESULTS: In ARM embryos, the neural tube was irregularly branched and formed an anomalous mass in the sacral region. Embryonal caudal somites differentiated into myogenic cells to form proper myotubes in the pelvis corresponding to the developmental stages between E12.5 and E15.0 both in affected embryos and the controls. CONCLUSIONS: In ARM embryos, an impaired anatomic framework of the pelvis was caused by neural maldevelopment, whereas muscle development proceeded physiologically. These results support the hypothesis that pelvic floor muscles may function in ARM children, in whom neural abnormalities such as meningomyelocele or tethered spinal cord have been ruled out, if the surgical correction is appropriately completed.
BACKGROUND/ PURPOSE: Recent biological studies have elucidated the molecular mechanism of muscle development, in which various regulatory molecules play key roles during embryogenesis. To determine possible myogenic abnormalities in anorectal malformations (ARM), the authors investigated the pelvic muscle development in murine embryos affected with ARM. METHODS: ARM embryos were induced by all-trans retinoic acid (ATRA) on the ninth gestational day (E9.0). Embryonal specimens were obtained from the uteri between E10.5 and E16.0, and the frozen sections were prepared for immunohistochemistry using antibodies specific for MyoD, myogenin, and PGP9.5 molecules. RESULTS: In ARM embryos, the neural tube was irregularly branched and formed an anomalous mass in the sacral region. Embryonal caudal somites differentiated into myogenic cells to form proper myotubes in the pelvis corresponding to the developmental stages between E12.5 and E15.0 both in affected embryos and the controls. CONCLUSIONS: In ARM embryos, an impaired anatomic framework of the pelvis was caused by neural maldevelopment, whereas muscle development proceeded physiologically. These results support the hypothesis that pelvic floor muscles may function in ARM children, in whom neural abnormalities such as meningomyelocele or tethered spinal cord have been ruled out, if the surgical correction is appropriately completed.
Authors: Christian Coarfa; Diego Florentin; NagiReddy Putluri; Yi Ding; Jason Au; Dandan He; Ahmed Ragheb; Anna Frolov; George Michailidis; MinJae Lee; Dov Kadmon; Brian Miles; Christopher Smith; Michael Ittmann; David Rowley; Arun Sreekumar; Chad J Creighton; Gustavo Ayala Journal: Prostate Date: 2017-11-13 Impact factor: 4.104