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RESCUE OF BROMODICHLOROMETHANE-INDUCED PREGNANCY LOSS IN THE F344 RAT BY EXOGENOUS PROGESTERONE AND HCG
Citation:
Bielmeier, S. R., D S. Best, AND M G. Narotsky. RESCUE OF BROMODICHLOROMETHANE-INDUCED PREGNANCY LOSS IN THE F344 RAT BY EXOGENOUS PROGESTERONE AND HCG. Presented at NIEHS/NTA Science and Career Fair, RTP, NC, May 10, 2002.
Description:
Rescue of bromodichloromethane-induced pregnancy loss in the F344 rat by exogenous progesterone and hCG.
Susan R. Bielmeier1, Deborah S. Best2 and Michael G. Narotsky2
1 Curriculum in Toxicology, Univ. of North Carolina, Chapel Hill, NC, USA
2 Reproductive Toxicology Division, NHEERL, USEPA, RTP, NC, USA
Previously, we reported that bromodichloromethane (BDCM), a drinking water disinfection by-product, causes pregnancy loss (i.e., full-litter resorption) in F344 rats when treated during the luteinizing hormone (LH)-dependent period. BDCM-induced pregnancy loss was associated with marked reductions in serum progesterone and corresponding decreases in LH on gestational day (GD) 10. Although an effect on luteal responsiveness has not been entirely ruled out, these findings strongly suggest that BDCM alters LH secretion, possibly via an effect on the hypothalamus or pituitary gland. Here, in order to provide further evidence of this mode of action, we attempted to rescue BDCM-exposed pregnancies with exogenous progesterone or human chorionic gonadotropin (hCG) , a LH-agonist. BDCM, in 10% aqueous Alkamuls, was dosed by oral gavage on GD 6-10 (plug day = GD 0) at 100 mg/kg/d in the F344 rat. Progesterone, dissolved in corn oil, was dosed at 10 mg/kg twice daily on GD 6-10 at 1 ml/kg via subcutaneous injection. In another test group, hCG in saline was dosed subcutaneously on GD 8?10 at 0.5 IU/rat in 0.2 ml. The rats were allowed to deliver and pups were examined postnatally. Cases of pregnancy loss were confirmed by staining uterine resorption sites with 10% ammonium sulfide. Both progesterone and hCG significantly prevented BDCM-induced pregnancy loss (p< 0.001). Dams dosed with BDCM on GD 6-10 and the hormone vehicles displayed a 70% pregnancy loss rate (7 of 10). Dams dosed with BDCM and progesterone had a 0% (0 of 8) incidence of pregnancy loss. Dams dosed with BDCM and hCG on GD 8-10 had an 11% (1 of 9) incidence of pregnancy loss. Since hCG, a LH agonist, prevented pregnancy loss when administered in conjunction with BDCM, a pituitary-mediated mechanism of pregnancy loss is suggested. These data further support the hypothesis that BDCM-induced pregnancy loss in the rat occurs via a LH-mediated mode of action.
[Funded by the EPA/UNC Toxicology Research Program, Training Agreement CT827206 Curriculum in Toxicology, UNC-Chapel Hill. This abstract does not necessarily reflect EPA policy.]