The potential relationship of maternal toxicity, general stress, and fetal outcome

Standard teratology bioassays generally call for a top dose level which is sufficient to induce some form of overt maternal toxicity such as death or weight loss. The presence of such maternal toxicity is often a confound in the interpretation of experimental results, especially at those dose levels producing the toxicity. While the physiological bases for the toxicity vary widely in a compound-related fashion, one underlying factor that remains constant for most induced toxicity is the presence of generalized stress in the affected animals. Previous studies have indicated that pregnant animals treated acutely with toxic levels of a variety of pharmacologically unrelated chemicals produced litters without a recognizable syndrome of defects, except for an increased incidence of supernumerary ribs (SNR). The present study reports on the effects of immobilization stress on the production of SNR in the Sprague-Dawley rat and the CD-1 mouse. Pregnant animals were immobilized in the supine position for 12-hour periods during the day of greatest sensitivity to SNR production (days 9 and 10 in the mouse and rat, respectively). Animals were killed immediately before term and the fetuses were examined. An increase in SNR was noted in immobilized mice but not rats. These results suggest that such fetal effects may be the result of general agent-induced maternal stress.