Teratogenic effects of hyperthermia in the bonnet monkey (Macaca radiata)

Seventeen timed‐mated bonnet monkeys (Macaca radiata) were exposed to hyperthermia in a forced‐draft incubator for a duration of one, three, four or eight days between 21 and 46 days of gestation. On each day of exposure the core temperature of the pregnant animal was elevated 2.4 to 5.4°C above the reference temperature recorded before heat exposure. Malformations occurred following a one‐hour daily elevation of the core temperature above the reference temperature under the following exposure conditions: 3.8°C, days 23 to 26; 3.9°C, days 24 to 27; 2.4°C, days 27, 28 and 30; and 4.1°C, day 26 of gestation. Five resorptions occurred following exposure for one, three or four days between days 24 and 29 of gestation after core temperature elevation of 3.7 to 4.4°C and three abortions occurred following exposure for four days between days 24 and 35 of gestation after core temperature elevation of 2.6 to 3.9°C. The results clearly indicate that the teratogenic sensitive period is from 23 to 30 days gestation following elevations of the core temperature from 2.4 to 4.1°C. No distinct pattern of malformations was observed although skeletal and umbilical cord malformations were the most common. Pathological changes in placental structure, expecially maternal surface infarctions and intervillous thrombi, were associated with three of the four abnormal fetuses, suggesting a relationship between pathological placental characteristics and fetal malformations in this study. The degree of core temperature elevation which resulted in malformations in the present study are similar to those applied to other mammalian species, and the specific anomalies observed in the bonnet monkey resemble those observed in other mammalian species, including man.