Is There an Optimal State for the Induction of Cleft Palate in the Mouse?

Abstract

It is well—known that each organ of the embryo passes through a period of development during which it is susceptible to the action of a teratogen. Since a certain malformation can be induced by various means, the question arises whether each teratogen has its own critical period for the production of such a defect. In the case of cleft palate, there is some evidence for the existence of different critical induction periods for different agents (5). For instance, Murakami (12) showed that irradiation of CF I mice on the eleventh day of pregnancy gave a higher incidence of embryos with cleft palate than when irradiation took place on any other day. On the other hand, Curley and co—workers (2), Who induced cleft palate with 6-aminonicotinamid e, found that the embryos were most sensitive to the action of the teratogen on the thirteenth day of pregnancy. Unfortunately the latter authors did not use the same strain of mice as Murakami. It is therefore difficult to compare their results, especially since Fraser (6) has shown that, in the A/Jax strain, the palate closes later than in the C57BL strain. This consideration made it of interest to repeat the experiments of Murakami and of Curley and his associates using one strain of mice only. It was also decided to extend the work of these authors by de— termining the period in which dexamethasone and cyclophosphamide could induce cleft palate. The teratogenic properties of these two drugs have been described respectively by Pinsky and'diGeorge (13) and by Gibson and Becker (7). The data collected during the investigation made it also possible to determine the sex ratio of embryos with cleft palate. According to Fogh-Andersen (4) and also Meskin and associates (10), the human female is more frequently born with a cleft than the male. Dagg and co-workers (3) found in mice more female than male fetuses with a cleft when the mothers had been treated with 5-fluorouracil. The question was The authors are affiliated with the