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PREGNANCY LOSS IN THE F344 RAT CAUSED BY BROMODICHLOROMETHANE: EFFECTS ON SERUM LUTEINIZING HORMONE LEVELS
Citation:
Bielmeier, S. R., D S. Best, AND M G. Narotsky. PREGNANCY LOSS IN THE F344 RAT CAUSED BY BROMODICHLOROMETHANE: EFFECTS ON SERUM LUTEINIZING HORMONE LEVELS. Presented at NIEHS/NTA Science and Career Fair, (NIEHS)RTP, NC, May 4, 2001.
Description:
PREGNANCY LOSS IN THE F344 RAT CAUSED BY BROMODICHLOROMETHANE: EFFECTS ON SERUM LUTEINIZING HORMONE LEVELS
Bielmeier1, S.R., D.S. Best2, and M.G. Narotsky2; 1University of North Carolina at Chapel Hill, Curriculum in Toxicology, 2Reproductive Toxicology Division, U.S. Environmental Protection Agency, Research Triangle Park, NC.
Previously, we demonstrated that bromodichloromethane (BDCM), a drinking water disinfection by-product, causes pregnancy loss in F344 rats when treated during the luteinizing hormone (LH)-dependent period [gestational days (GD) 7-10]. The pregnancy loss, i.e. full-litter resorption (FLR), was associated with reduced serum progesterone levels; however, using a radioimmunoassay, we were unable to show an effect on LH. Here, we re-evaluate serum LH levels using the more sensitive dissociation-enhanced lanthanide flourometric immunoassay (DELFIA?). BDCM, in 10% emulphor, was dosed at 75 mg/kg/d by gavage on GD 6-10. Blood samples were collected once daily on GD 6-11. The rats were allowed to deliver and pups were examined. All control dams successfully maintained their litters, whereas 88% (seven of eight) of the BDCM-treated dams had FLR. In controls, serum progesterone levels were >100 ng/ml throughout the study. Serum LH levels in these dams were generally >0.11 ng/ml until GD 11, at which time all values were 0.08 ng/ml. In contrast, treated dams with FLR had significantly reduced progesterone levels on GD 10; all values were <40 ng/ml. Serum LH levels were also significantly reduced on GD 10; mean ? SE values were 0.08 ? 0.03 ng/ml, vs. 0.15 ? 0.02 ng/ml for controls. Thus, BDCM-induced pregnancy loss was associated with marked GD-10 reductions in serum progesterone and corresponding decreases in LH. Although an effect on luteal responsiveness has not been entirely ruled out, these new findings strongly suggest that BDCM alters LH secretion, possibly via an effect on the hypothalamus or pituitary gland.
[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.]