Aspirin pretreatment potentiates hyperthermia-induced teratogenesis in the mouse

Objective: Our purpose was to investigate the effect of aspirin pretreatment on hyperthermia-induced teratogenesis. The rationale for the study was based on the growing evidence that prostaglandin pathway may be involved in the cellular response to the thermic injury. Study Design: 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 bath treatment at 38° C, 41° C, 42° C, or 43° C. On gestation day 18 uterine contents were evaluated for developmental disorders, including prenatal mortality, intrauterine growth restriction, and external, visceral, and skeletal abnormalities. Results: Consistent with expectations, hyperthermia impaired morphogenesis in a dose-related manner. Although aspirin alone did not reveal embryotoxicity, its administration potentiated hyperthermia-induced teratogenesis. A statistically significant interaction (p<0.05) was observed at 42° C, where the incidence of fetuses per litter with axial skeletal malformations increased from 20.3% to 55.7%. Conclusion: A nonteratogenic dose of aspirin enhanced the teratogenic response to hyperthermia. This result fits the hypothesis that prostaglandins may play a protective role in hyperthermia-induced teratogenesis.