Influence of the drinking water disinfection by-product dibromoacetic acid on rat estrous cyclicity and ovarian follicular steroid release in vitro.

The drinking water disinfection by-product, dibromoacetic acid (DBA) has been reported to affect gonadal functions in the male rat. However, there is little information regarding the influence of DBA on female reproductive activity. Consequently, the present study investigated the effects of DBA on estrous cyclicity and the impact in vitro of DBA on ovarian follicular steroid secretion. Regularly cycling animals were dosed with DBA (0 to 270 mg/kg/day) for 14 days and estrous cyclicity was monitored during treatment and for an additional 2-week posttreatment interval. A dose-related alteration in cyclicity was observed at 90 and 270 mg/kg/day, which persisted through the posttreatment monitoring in the high dose group. An in vitro exposure of preovulatory follicles to DBA was then used to assess the influence of DBA on steroid release. To select a concentration for use, a single oral exposure to 270 mg/kg was administered, and the mean blood levels were determined over a 5-h interval. For this in vitro work, pairs of preovulatory follicles from PMSG-primed immature rats were exposed to 0 or 50 microg/mL DBA over a 24-h period and evaluated for estradiol and progesterone release under baseline and hCG-stimulated conditions. The influence of tumor necrosis factor (TNFalpha) exposures under these conditions was also determined. In the nonstimulated condition, DBA was found to increase the release of estradiol, but had no detectable effect in response to hCG. Progesterone, however, showed marked suppression under hCG stimulation following exposure to DBA, while nonstimulated secretion was unaffected. TNFalpha by itself also suppressed stimulated progesterone release, but had no additional effect in combination with DBA. The data suggest that one factor in the disruption in estrous cyclicity could be an alteration in steroid production, which was characterized by separate effects on both estradiol and progesterone secretion.