ASPIRIN PRETREATMENT POTENTIATES HYPERTHERMIA-INDUCED TERATOGENESIS IN THE MOUSE

OBJECTIVE: Our purpose was to investigate the effect of aspirin pretre atment on hyperthermia-induced teratogenesis. The rationale for the st udy was based on the growing evidence that prostaglandin pathway may h e involved in the cellular response to the thermic injury. STUDY DESIG N: On gestation day 8.5 Swiss mice were treated with 0 or 200 mg/kg of aspirin and 1 hour later exposed to a single 10-minute thermostatic b ath treatment at 38 degrees C, 41 degrees C, 42 degrees C, or 43 degre es C. On gestation day 18 uterine contents were evaluated for developm ental disorders, including prenatal mortality, intrauterine growth res triction, and external, visceral, and skeletal abnormalities. RESULTS: Consistent with expectations, hyperthermia impaired morphogenesis in a dose-related manner. Although aspirin alone did not reveal embryotox icity, its administration potentiated hyperthermia-induced teratogenes is. A statistically significant interaction (p <0.05) was observed at 42 degrees C, where the incidence of fetuses per litter with axial ske letal malformations increased from 20.3% to 55.7%. CONCLUSION: A nonte ratogenic dose of aspirin enhanced the teratogenic response to hyperth ermia. This result fits the hypothesis that prostaglandins may play a protective role in hyperthermia-induced teratogenesis.