Morphologic analysis of the neuromuscular development of the anorectal unit in fetal rats with retinoic acid induced myelomeningocele.
To investigate whether myelomeningocele (MMC) is associated with a global neuromuscular maldevelopment of the lower gastrointestinal (GI) tract and anorectum, the distribution and staining intensity of non-neuronal (alpha-smooth-muscle-actin), neural crest cell (NCC, [Hoxb5]), and neuronal markers (PGP-9.5, synaptophysin, neurotubulin-beta-III) within the distal colon, rectum, and anal sphincters were analyzed by immunohistochemistry and Western blot in rat fetuses with retinoic acid (RA) induced MMC. At term (E22), no gross-morphological differences of the anorectal unit of OIL (n=21) MMC (n=31), and RA-exposed-non MMC (RA, n=19) fetuses were found. Smooth muscle cells were evenly distributed within the muscle layers of the rectum and the internal anal sphincter in OIL, MMC, and RA fetuses. Density and staining intensity of NCC and mature enteric neurons within the myenteric plexus of the distal colon and rectum and innervation pattern within anal sphincters in MMC fetuses were analogous to RA and OIL controls. Normal smooth muscle and myenteric plexus development of the rectum and normal innervation of the anal sphincters and pelvic floor suggests that MMC is not associated with a global neuromuscular maldevelopment of lower GI structures in this short-gestational model.
The Children's Center for Fetal Research, Children's Hospital of Philadelphia, The University of Pennsylvania School of Medicine, Abramson Research Center, Room 1116B, 3615 Civic Center Boulevard, Philadelphia, PA 19104-4318, USA.
Enrico
E
Danzer
Antoneta
A
Radu
Lauren E
LE
Robinson
MaryAnn V
MV
Volpe
N Scott
NS
Adzick
Alan W
AW
Flake
D000818:Animals; D004622:Embryo, Mammalian; D005260:Female; D018398:Homeodomain Proteins / Q000378:metabolism; D007420:Intestine, Large; D008591:Meningomyelocele / Q000139:chemically induced / Q000473:pathology* / Q000503:physiopathology; D009130:Muscle, Smooth / Q000294:innervation / Q000473:pathology; D009469:Neuromuscular Junction / Q000196:embryology* / Q000473:pathology*; D011247:Pregnancy; D051381:Rats; D016708:Synaptophysin / Q000378:metabolism; D014212:Tretinoin; D014404:Tubulin / Q000378:metabolism; D043222:Ubiquitin Thiolesterase / Q000378:metabolism
D018398:Homeodomain Proteins; D016708:Synaptophysin; D014404:Tubulin; C029575:neurotubulin; D014212:Tretinoin; C489034:UCHL1 protein, rat; D043222:Ubiquitin Thiolesterase