Evidence that the notochord may be pivotal in the development of sacral and anorectal malformations.
OBJECTIVE
The notochord is known to organize normal development of central axial structures, such as the spinal cord, vertebral column, and anorectum, but its role in abnormal development of these organs has not been well documented. The current study has used Ethylenethiourea to induce anorectal malformations in fetal rats, allowing investigation of abnormalities of the notochord and their relationship to the axial structural abnormalities that occur.


METHODS
Timed-mated pregnant rats were fed Ethylenethiourea by gavage on gestational day 10. Their embryos were harvested on gestational days 13 to 16 and sectioned in either the transverse or sagittal plane. Sections were stained with H and E and examined serially.


RESULTS
Anorectal malformations were identified in 29 of 34 embryos and neural tube defects in 24, ranging from an accessory neural tube to lumbo-sacral rachischisis. There was no tail or only a rudimentary tail in the majority of embryos. Abnormalities of the notochord in the lumbo-sacral area included ventro-dorsal branching, ventral deviation, and ectopic notochordal tissue. Most abnormal notochord branches and ectopic notochordal tissue were abnormally close to or in contact with the wall of the cloaca or neural tube.


CONCLUSIONS
Given the known role of the notochord in controlling normal development, this study would suggest that abnormal notochord development may be pivotal in producing neural tube defects and anorectal malformations, possibly by altering sonic hedgehog signalling.
Qi
Bao Quan
BQ
Department of Paediatric Surgery Christchurch Hospital, Christchurch, New Zealand.
Beasley
Spencer W
SW
Frizelle
Francis A
FA
D001003:Anal Canal / Q000002:abnormalities / Q000196:embryology; D000818:Animals; D004065:Digestive System Abnormalities / Q000139:chemically induced / Q000196:embryology*; D004195:Disease Models, Animal; D005031:Ethylenethiourea; D009436:Neural Tube Defects / Q000139:chemically induced / Q000196:embryology*; D009672:Notochord / Q000196:embryology*; D038081:Organogenesis; D051381:Rats; D013116:Spinal Cord / Q000002:abnormalities / Q000196:embryology; D013131:Spine / Q000002:abnormalities / Q000196:embryology
D005031:Ethylenethiourea