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.

Endocrine-disrupting chemicals: prepubertal exposures and effects on sexual maturation and thyroid activity in the female rat. A focus on the EDSTAC recommendations.

In 1996, the US Environmental Protection Agency was given a mandate by Congress to develop a screening program that would evaluate whether variously identified compounds could affect human health by mimicking or interfering with normal endocrine regulatory functions. Toward this end, the Agency chartered the Endocrine Disruptor Screening and Testing Advisory Committee in October of that year that would serve to recommend a series of in vitro and in vivo protocols designed to provide a comprehensive assessment of a chemical's potential endocrine-disrupting activity. A number of these protocols have undergone subsequent modification by EPA, and this review focuses specifically on the revised in vivo screening procedure recommended under the title Research Protocol for Assessment of Pubertal Development and Thyroid Function in Juvenile Female Rats. Background literature has been provided that summarizes what is currently known about pubertal development in the female rat and the influence of various forms of pharmaceutical and toxicological insult on this process and on thyroid activity. Finally, a section is included that discusses technical issues that should be considered if the specified pubertal endpoints are to be measured and successfully evaluated.

Evidence for the presence of tumor necrosis factor alpha receptors during ovarian development in the rat.

Tumor necrosis factor alpha (TNFalpha) is an intraovarian cytokine that may play a role in ovarian development and function. Effects of TNFalpha are mediated by binding to at least one of two TNFalpha receptor subtypes (with molecular masses of approximately 60 and 80 kDa); therefore, the overall goal of this study was to determine whether rat ovaries have TNFalpha receptors during critical times in development. Two approaches were used: 1) demonstration of specific binding of radiolabeled TNFalpha to ovarian cells and 2) semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) analysis for each of the two TNFalpha receptors. Ovarian cells were obtained on Embryonic Day 19, day of birth (Day 0), and Days 2, 5, 10, and 20. TNFalpha binding was present on all days, with significantly greater binding on Day 20. Messenger RNA for both receptor subtypes was detected on all days using RT-PCR analysis but was significantly greater for the 60-kDa receptor on Day 20. In conclusion, rat ovaries contained receptors capable of binding TNFalpha and mRNA for both receptor subtypes. Identification of ovarian TNFalpha receptors provides support for a role of TNFalpha in ovarian development and function.