A comparative study of the effects of retinoic acid given during the critical period for inducing spina bifida in mice and hamsters.

Spina bifida occurred in the offspring of golden Syrian hamsters treated on day 8 of gestation, and CD-1 mice treated on day 9, with 80 mg/kg of retinoic acid. Light microscopic examination of term fetuses demonstrated that myeloschisis was the characteristic form of the defect in mice, whereas myelocystocele was the predominant type of spina bifida induced in the hamster. To investigate the pathogenesis of these defects, a comparative study was undertaken by light microscopy and scanning electron microscopy of the changes occurring in caudal embryonic tissues during the initial 48 hr following maternal treatment. Within 18 hr of exposure, similar effects were observed in both species. These included distortion of the neural folds at the level of the posterior neuropore, vascular damage and hematoma formation, malformation of the notochord, and abnormalities of secondary neurulation. No differences were observed that we thought could account for the apparent variation in the pattern of malformations seen in the term litters. Rather, the dissimilarity may reflect species differences in the position of the posterior neuropore in the neuraxis and in the extent to which secondary neurulation contributes to the development of the lumbosacral cord segments.