Malformations of the eye resulting from maternal hypervitaminosis A during gestation in the rat

Vitamin A (1--1.5 lac IU) was administered orally to pregnant Wistar rats on days 8--14 of gestation (sperm + = day 0). Fetuses collected on day 21 revealed several anomalies including those of the eyes, e.g. open eyelids, exophthalmia, cataractous lens, microphthalmia and anophthalmia. Histological examination of treated eyes revealed degenerative changes in the cornea, lens and retina; shallowness or obliteration of anterior and vitreous chambers, and complete fusion of various structures with each other in some cases of microphthalmia. Anophthalmic cases showed no trace of any ocular structure. Retinae showed remarkable infoldings. The degenerative changes in retinae were associated with degeneration of optic nerve fibres. Eye malformations induced by hypervitaminosis A were stage dependent and mostly found in groups treated on day 8 and 9 of gestation. Reported cases of anomalies in humans associated with hypervitaminosis A during pregnancy warn us against the uncritical use of high doses of vitamin A during pregnancy.