On embryonic day 21, pregnant guinea pigs were exposed to a 44 degrees C environment for 1 hour. As a result, all brain ventricular zone cells in M phase of the mitotic cycle when heat-shock occurred became immediately pyknotic and all cell division was stopped for 4-8 hr. The pyknotic cells were removed at a definable rate until mitosis resumed, after which removal occurred in an apparently random manner. Long delays in the return to mitosis were related to increased destruction of S-phase cells deep within the ventricular zone and largely confined to the alar lamina. Upon recovery, a rostrocaudal delay in mitosis was apparent, and the number of mitotic figures was increased compared with control numbers for 1 hr, after which they returned to control numbers. It was evident that up to 40% of the cells within the ventricular zone were destroyed following brief maternal heat stress.

Guinea pigs were exposed to hyperthermia for 1 hr once or twice on day 11, 12, 13, or 14 (E11-E14) of pregnancy. The mean rectal temperatures were elevated by 3.4 degrees C-4.0 degrees C. This treatment resulted in a marked elevation of rates of resorption and developmental defects in embryos examined at day E23. The defects observed were those affecting the neural tube (NTD) (exencephaly, encephaloceles, and microphthalmia), kyphosis/scoliosis, branchial arch defects, and pericardial edema. Embryos with NTD and kyphosis/scoliosis have not been found among newborn guinea pigs to date following maternal heat exposure on days E12-E14. It appears that embryos with these defects are filtered out by resorption or abortion by days E30-E35.

In our recent studies on the effects of maternal hyperthermia on the embryonic guinea-pig, we have demonstrated two 'teratogenic windows' at embryonic days 13 and 21 (E13 and E21). E13 encompasses the period of the closure of the neural groove and anterior neuropore, and E21 the commencement of the cortical plate. The approximate equivalent developmental times in the human are E23-E25 and E49-E56 respectively. In the guinea-pig, maternal hyperthermia at E13 results in a high incidence of neural tube defects (NTD), many open, and associated with other defects such as microphthalmia, and scoliosis or kyphosis. The NTD were most common in the developing hindbrain and all demonstrated considerable infoldings of neural tissue, rosettes of neuroepithelial cells, outpocketings of neural tissue and large cystic cavities beneath the defect. In human examples from the Kyoto Human Embryo Collection, 16 had verified hyperthermic insults at E23-E25 and all had NTD which showed similar deformities to the guinea-pig. Most embryos with such gross defects are aborted in the early fetal period in both species.

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