Induction of cleft palate in mice by inhibitors of prostaglandin synthesis.

The present study investigates the effects of several nonsteroidal anti-inflammatory drugs on mouse palatal fusion in vivo and in vitro. Five different nonsteroidal anti-inflammatory agents were injected into pregnant mice of the AKR-strain on day 13.5 of gestation. Paired palatal processes from 13.5- and 14.5-day-old mouse embryos were organ-cultured for 72 hours in control and anti-inflammatory drug-containing media. Each experimental group of animals and explants received one of the following drugs: naproxen, sulindac, indomethacin, diclofenac, and mefenamic acid. Drug treatment induced different frequencies of cleft palate in the offspring. The most teratogenic drug was sulindac, and indomethacin was almost ineffective. In vitro each drug prevented fusion of the palatine processes in treated explants, and the degree of inhibition was dependent on the stage of development at the time of explanation. In both the in vivo and in vitro experiments, the drugs prevented medial epithelial cell breakdown that normally occurs in the medial secondary palatal epithelium. The results obtained in the present study suggest that prostaglandins may play an important role in normal differentiation of the developing palatine region.