2-bromopropane causes ovarian dysfunction by damaging primordial folliclesand their oocytes in female rats

Ovarian dysfunction induced by 2-bromopropane (2-BP) has been described in female factory workers and experimental animals. However, the underlying me chanism is still unclear. To establish the reproductive target site and def ine mechanisms of 2-BP toxicity in adult female rats, we examined the effec ts of different doses and duration of exposure to 2-BP in female rats. In t he dose-dependent experiments, female rats were exposed to 2-BP at 100, 300 , or 1000 ppm or fresh air (n = 9 each) in exposure chambers for 8 h/day fo r 9 weeks. In the time-course experiments, female rats were exposed to 2-BP at 3000 ppm for 8 h (n = 7 each). The rats were then euthanized 1, 3, 5, a nd 17 days after exposure. Differential follicle counts and in situ termina l deoxynucleotidyl transferase assay were used to evaluate 2-BP effect on p rimordial, growing, and antral follicles. Exposure to 2-BP at 300 and 1000 ppm produced a significant reduction in the percentage of primordial, growi ng, and antral follicles in a dose-dependent manner. Significant reduction in the percentage of primordial follicles at 17 days after exposure was obs erved in time-course experiments. Exposure to 2-BP at 3000 ppm for 8 h resu lted in histological changes in primordial follicles complex at 5 and 17 da ys after exposure. These changes consisted of distortion of the symmetry of oocytes and their nuclei at Day 5 after exposure and appearance of eccentr ic pyknotic cells and shrinkage of oocyte nuclei at Day 17 after exposure. In situ end labeling showed increased numbers of apoptotic oocytes and gran ulosa cells in primordial follicles at Days 5 and 17 after exposure. Our re sults suggested that ovarian dysfunction induced by 2-BP was caused by the destruction of primordial follicle and its oocyte due to the induction of a poptosis. Our studies also show that the follicle differential count is a m ore sensitive method than the vaginal smear in monitoring the female reprod uctive disorders induced by 2-BP. (C) 1999 Academic Press.