PARENT SESSION
Pregnancy and Parturition

PREGNANCY LOSS IN THE F344 RAT CAUSED BY BROMODICHLOROMETHANE: EFFECTS ON SERUM LUTEINIZING HORMONE LEVELS.

Bielmeier, Susan¹, Best, Deborah ², Narotsky, Michael², ^{1 2}

ABSTRACT- 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]. We reported that 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. In this study, we re-evaluated serum LH levels using a more sensitive assay. BDCM, in 10% emulphor, was dosed at 75 mg/kg/d by gavage to F344 rats on GD 6-10 (plug day = GD 0). Blood samples were collected from the lateral tail vein once daily on GD 6-11. Serum progesterone was measured by ELISA, and LH was measured using a dissociation-enhanced lanthanide flourometric immunoassay (DELFIA®). The rats were allowed to deliver and pups were examined on postnatal days 1 and 6. Cases of FLR were confirmed by staining uterine resorption sites with 10% ammonium sulfide. All nine 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, all BDCM-treated dams with FLR had significantly reduced progesterone levels on GD 10; all values were <40 ng/ml. Serum LH levels in these animals were also significantly reduced on GD 10, with five of seven dams having values below the detection limit (0.03 ng/ml); 0.08 ± 0.03 ng/ml, vs. 0.15 ± 0.02 ng/ml for controls. On GD 11, dams with FLR had increased LH levels. Thus, BDCM-induced pregnancy loss was associated with marked GD-10 reductions in serum progesterone and corresponding decreases in LH. The sensitivity of the DELFIA technique enabled us to demonstrate this previously undetected effect on 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.]

KEY WORDS: bromodichloromethane, disinfection by-product, pregnancy loss, luteinizing hormone