The induction of microphthalmia, encephalocele, and other head defects following hyperthermia during the gastrulation process in the rat.
The aim of this study was to ascertain whether there is a period during early embryonic development of the rat that is particularly sensitive to hyperthermia. Pregnant Sprague-Dawley rats were partially immersed in a water bath at 43.5 degrees C until their core temperatures, monitored by a rectal thermistor probe, were elevated to 43.5 degrees C. The procedure was repeated 6 hours later. The regimen of two heatings was performed over a range of development from early gastrulation (8 days 18 hours) to about the 12 somite stage (10 days 18 hours). The rats were killed on days 17-19 and the fetuses were examined. Each group contained a minimum of five litters. The main teratogenic effect of the hyperthermia was the induction of one or more head defects, notably microphthalmia, encephalocele (either a single, large, parietal encephalocele or multiple small protuberances), and maxillary hypoplasia. Microphthalmia was the most common defect with approximately 90% of surviving fetuses having small eyes when heating occurred between 9 days 6 hours and 10 days 0 hours (9.06 and 10.00). Encephaloceles were induced by heating between 9.00 and 10.00 with a peak sensitivity between 9.12 and 9.18 when 57% of surviving fetuses were affected. Maxillary hypoplasia resulted from heating between 9.06 and 10.06 with up to 20% of surviving fetuses being affected. Control rats were exposed to the same experimental procedure in a water bath at 38 degrees C on 9.12 and 9.18, the gestational time most sensitive to hyperthermia induced malformations. There were no abnormal fetuses in the controls. The critical period identified spans 9 days 6 hours to 10 days 0 hours gestational age. In developmental terms this includes a large proportion of the gastrulation process.
D000818:Animals; D020964:Embryo Loss / Q000209:etiology; D004622:Embryo, Mammalian; D004677:Encephalocele / Q000196:embryology / Q000209:etiology*; D005260:Female; D005334:Fever / Q000150:complications* / Q000196:embryology; D005775:Gastrula / Q000502:physiology*; D006257:Head / Q000002:abnormalities*; D008437:Maxilla / Q000002:abnormalities; D008850:Microphthalmos / Q000196:embryology / Q000209:etiology*; D011247:Pregnancy; D011248:Pregnancy Complications; D051381:Rats; D011919:Rats, Inbred Strains