Pregnancy Alterations Following Xenobiotic-Induced Delays in Ovulation in the Female Rat

Abstract

Pregnancy Alterations Following Xenobiotic-Induced Delays in Ovulation in the Female Rat. Cooper. R. L., Barrett, M. A., Goldman, J. M., Rehnberg, G. L., McElroy, W. K., and Stoker, T. E. (1994). Fundam. Appl. Toxicol. 22, 474-480.Chlordimeform [N′-(4-chloro-o-tolyl)-N,N-dimethylformamidine] has been shown to cause a 1-day delay in the surge of luteinizing hormone (LH) in ovariectomized, steroid-primed female rats, presumably through its ability to block CNS α-noradrenergic receptors and consequently CNS regulation of anterior pituitary function. In the present study, we determined whether a chlordimeform-induced delay in the ovulatory surge of LH would alter pregnancy outcome in intact females. Chlordimeform (50 mg/kg) or sodium pentobarbital (35 mg/kg), as a positive control, was administered in order to delay ovulation 24 (1-day delay) or 48 hr (2-day delay). Females were then housed with proven fertile males on the evening of proestrus (0-day delay group), the following evening (1-day delay group), or the evening after that (2-day delay group). The number of receptive females in each group, the mean lordosis quotient, and the number of sperm-positive females in each group were recorded. All females were killed on Gestation Day 20. The number of pregnant females in the 1- or 2-day delay groups was reduced with both chlordimeform and pentobarbital. Also, delaying ovulation for 1 or 2 days with either compound resulted in a significant reduction in the number of live pups present on Gestation Day 20 and a decrease in the number of implantation sites. Litter size was not affected if the females were mated on the same day that treatment was administered (0-day delay). Pentobarbital did not alter the proportion of females showing sexual behavior or the mean lordosis quotient in the 0- and 1-day delay groups, although fewer 1-day females were sperm positive. The number of sexually active and sperm-positive females was reduced in the 2-day pentobarbital-delayed group. However, the lordosis quotient of those that were sexually active was not different than that of control. Similarly, in CDF-treated groups, the proportion of females showing sexual activity was reduced in the 0- and 2-day delayed groups. In contrast, sexual behavior was lower in the 0-day delayed females when tested 2 hr after lights out. These females did eventually mate, however, as confirmed by the high incidence of sperm positive smears the following morning. The number of sperm positive females was lower in both the 1- and 2-day chlordimeform-induced delay groups. Thus, brief exposures to compounds such as formamidine pesticide chlordimeform will result in not only a delay in breeding but, more importantly, a significant reduction in litter size.