SKELETAL DEVELOPMENT FOLLOWING HEAT EXPOSURE IN THE RAT

The effects of gestation day (GD) 10 heat exposure in the rat were studied to determine the temperature-response relationship for the induction of skeletal and other defects. Conscious pregnant rats (Experiment 1) were exposed to various temperatures in a warm air chamber. Body temperature was measured using a rectal probe, and these measurements were confirmed as representing core body temperature in separate animals using telemetric procedures. Those animals whose core body temperature was raised to 41-41.9-degrees-C had over 90% malformed pups (examined at postnatal day (PND) 3), and a 25% reduction in the percent of live pups per litter. Animals whose temperature was raised to 39.2-40.9-degrees-C had a low incidence of pups with similar types of malformations. The primary types of malformations were of the axial skeleton, consisting of fusions and other abnormalities of the ribs and vertebral elements, and a decrease in the total number of ribs and centra. The acute maternal effects of these temperature increases were signs of heat exhaustion during and 1-2 hr after exposure, but there were no permanent changes in weight gain or other signs. When temperatures were raised to greater-than-or-equal-to 42-degrees-C, all maternal animals died. In a second study (Experiment 2), pregnant rats (from a different supplier) were anesthetized to determine the effect of reducing maternal stress and were exposed to heat as in Experiment 1. Those animals whose core body temperature was raised to 42-42.5-degrees-C for 5 min had pups with similar responses to those in Experiment 1 at 41-41.9-degrees-C, although the reduction in litter size was not as great. Animals whose temperature was raised to 41-degrees-C had a much lower incidence of pups with similar defects, and animals whose temperature was raised to 43-degrees-C did not survive. A more detailed analysis of the skeletal defects in Experiment 2 showed rib and vertebral malformations that appear to be related to the stage of somite development at the time of exposure.