The heat shock response: potential to screen teratogens.

ABSTRACT

The embryonic stress hypothesis of teratogenesis suggests that a proportion of all human congenital defects is due to a failure in essential gene transcription along with translational pre-emption by the heat shock response (HSR). We sought to determine the potential usefulness of the murine HSR to screen agents suspected of being human teratogens. The teratogenic potential of a selected group of known teratogenic (hyperthermia, insulin, retinoic acid and valproic acid) or non-teratogenic (cycloheximide, dinitrophenol and tetracycline) agents were administered to pregnant SWV mice at critical periods of neural tube closure. Following exposure to either teratogenic doses or at the highest dose possible that did not induce maternal toxicity for those compounds that were not teratogenic, the induction of heat shock protein (hsp) synthesis and changes in total protein synthesis were determined in lymphocytes isolated from murine spleens. The varied results obtained in these studies cast doubt on the value of the murine HSR to screen teratogens.