Developmental study of tethered spinal cord in murine embryos with anorectal malformations.
OBJECTIVE
Tethered spinal cord is frequently associated with anorectal malformations (ARMs). However, it remains unknown how the tethered spinal cord develops and relates to the severity of ARM. We studied the development of the spinal cord in ARM mouse embryos induced by all-trans retinoic acid (ATRA).


METHODS
Pregnant ICR-Slc mice were administered 100 mg/kg of ATRA on the ninth embryonic day (E9.0). Embryonic specimens were obtained from the uteri between E11.0 and E18.5. Midsagittal histologic sections focusing on the spinal cord and pelvis were prepared for immuonhistochemistry specific for neurofilament and Protein Gene Product 9.5 molecules.


RESULTS
More than 98% of ATRA-treated embryos demonstrated ARM with rectourethral or rectocloacal fistula. Normal embryos exhibited progressive ascent of the spinal cord from E14.5. However, in ARM embryos, the distal spinal cord ended with meningomyelocelelike or atypical hamartomatous lesions at E11.5 to E13.5, which later caused stretch force that damaged the spinal cord, resulting in tethered cord between E16.0 and E16.5.


CONCLUSIONS
In ATRA-induced ARM mouse embryos, tethered spinal cord was mostly established, accompanied by caudal neural maldevelopment, during early fetal development. This experimental model may be useful for researching detailed neuropathologic conditions in ARM children accompanied with tethered spinal cord.
Tsuda
Tomoki
T
Division of Surgery, Children's Research Hospital, Kyoto Prefectural University of Medicine, Kyoto 602-0841, Japan. tom@koto.kpu-m.ac.jp
Shimotake
Takashi
T
Aoi
Shigeyoshi
S
Kume
Yoko
Y
Deguchi
Eiichi
E
Iwai
Naomi
N
D000015:Abnormalities, Multiple / Q000503:physiopathology*; D001003:Anal Canal / Q000002:abnormalities*; D000818:Animals; D004195:Disease Models, Animal; D047108:Embryonic Development; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008813:Mice, Inbred ICR; D009153:Mutagens; D009436:Neural Tube Defects / Q000473:pathology* / Q000503:physiopathology; D011247:Pregnancy; D012007:Rectum / Q000002:abnormalities*; D014212:Tretinoin
D009153:Mutagens; D014212:Tretinoin