Kimmel C A, Cuff J M, Kimmel G L, Heredia D J, Tudor N, Silverman P M, Chen J
Reproductive and Developmental Toxicology Branch, U.S. Environmental Protection Agency, Washington, DC 20460.
Teratology. 1993 Mar;47(3):229-42. doi: 10.1002/tera.1420470307.
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 > or = 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.
研究了妊娠第10天热暴露对大鼠的影响，以确定诱导骨骼及其他缺陷的温度-反应关系。清醒的怀孕大鼠（实验1）在暖空气室中暴露于不同温度下。使用直肠探头测量体温，并通过遥测程序在单独的动物中确认这些测量值代表核心体温。那些核心体温升高到41-41.9摄氏度的动物，有超过90%的幼崽畸形（在出生后第3天检查），每窝活幼崽的百分比降低了25%。体温升高到39.2-40.9摄氏度的动物，出现类似畸形类型的幼崽发生率较低。主要的畸形类型是轴骨骼畸形，包括肋骨和椎骨元素的融合及其他异常，以及肋骨和椎体总数减少。这些温度升高对母体的急性影响是暴露期间及暴露后1-2小时出现热衰竭迹象，但体重增加或其他体征没有永久性变化。当温度升高到≥42摄氏度时，所有母体动物死亡。在第二项研究（实验2）中，对怀孕大鼠（来自不同供应商）进行麻醉以确定减轻母体应激的效果，并像实验1那样使其暴露于热环境中。那些核心体温升高到42-42.5摄氏度并持续5分钟的动物，其幼崽的反应与实验1中核心体温为41-41.9摄氏度的动物相似，尽管窝仔数的减少没有那么大。体温升高到41摄氏度的动物，出现类似缺陷的幼崽发生率要低得多，而体温升高到43摄氏度的动物未能存活。对实验2中骨骼缺陷的更详细分析表明，肋骨和椎骨畸形似乎与暴露时体节发育阶段有关。
