VITAMIN A TERATOGENESIS IN A SENSITIVE GENETIC BACKGROUND

Abstract

The critical event in lip formation is the convergence of the facial prominences. A variety of teratogens are known to interfere with later stages of facial prominence formation, and certain inbred mouse strains are known to be more susceptible to such teratogenic effects. Recently, we observed an otherwise normal child with severe bilateral cleft lip and palate. The mother took 50,000 iu of Vitamin A (one 25,000 iu Aquasol capsule bid) for 20 days between the 3rd and 6th week after conception, and the father had a unilateral cleft lip. To test the hypothesis that this may represent a teratogenic effect in combination with a sensitive genetic background, vitamin A was administered to A/J mice and 2 other inbred strains just prior to normal lip closure. A/J, IlWh, and SWFr mice were given 200 iu per gram vitamin A (retinyl palmitate) by gastric lavage at either 9:00 a.m. or 1:00 p.m. on day 9 (equivalent to 26-30 days gestation in the human). The frequency of cleft lip observed was not significantly different from the spontaneous frequency in the A/J strain, but there was a marked increase in the frequency and severity of cleft palate. Other inbred strains were not affected by cleft lip, and there was a less dramatic increase in the incidence of cleft palate in those strains. We conclude that the genetic background of the parents may be an important factor in evaluating risks for teratogenetic outcomes.