Hyperthermia as a teratogen: parameters determining hyperthermia-induced head defects in the rat

Teratology. 1985 Apr;31(2):265-72. doi: 10.1002/tera.1420310212.

Abstract

This study determined the relationship between the duration and extent of temperature elevation, during a critical period of rat embryonic development, and the induction of congenital malformations. Pregnant Sprague-Dawley rats, at 9 days 12 hours gestation (gastrulation stage), were partially immersed in a water bath until their core temperature, monitored by a rectal thermistor probe, was elevated to a nominated temperature. Seven temperatures were tested from 40.5 degrees C to 43.5 degrees C, elevations of 2.0-5.0 degrees C in core temperature. Various durations at each of these temperatures were tested for potential teratogenicity. A single elevation of 5.0 degrees C or 4.5 degrees C needed only a "spike" in duration to be teratogenic, 4.0 degrees C was teratogenic within 5 minutes, 3.5 degrees C within 10 minutes, 3.0 degrees C within 20 minutes, and 2.5 degrees C within 1 hour. An elevation of 2.0 degrees C for 8 hours was not teratogenic. Microphthalmia was the most common malformation at all teratogenic temperatures and was frequently the only malformation seen at the shortest time exposure for a particular temperature. Encephalocele, facial clefting, and maxillary hypoplasia were the other frequently seen malformations. Five control rats were placed in the water bath for 2 hours at 38 degrees C so that their core temperature was not elevated. All the control fetuses were normal. An elevation of 2.5 degrees C for 1 hour was the threshold combination for teratogenesis. As the temperature increased above a 2.5 degrees C elevation the necessary duration of exposure for teratogenesis decreased.

MeSH terms

  • Animals
  • Body Temperature
  • Cleft Lip / etiology
  • Cleft Palate / etiology
  • Congenital Abnormalities / etiology*
  • Encephalocele / etiology
  • Female
  • Gestational Age
  • Hot Temperature / adverse effects*
  • Maxilla / abnormalities
  • Microphthalmos / etiology
  • Pregnancy
  • Rats
  • Rats, Inbred Strains
  • Time Factors