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EFFECTS OF BROMODICHLOROMETHANE (BDCM) ON EX VIVO LUTEAL FUNCTION IN THE F344 RAT
Citation:
Bielmeier, S. R., A S. Murr, D S. Best, J M. Goldman, AND M G. Narotsky. EFFECTS OF BROMODICHLOROMETHANE (BDCM) ON EX VIVO LUTEAL FUNCTION IN THE F344 RAT. Presented at NC Society of Toxicology, RTP, NC, February 22, 2003.
Description:
EFFECTS OF BROMODICHLOROMETHANE (BDCM) ON EX VIVO LUTEAL FUNCTION IN THE PREGNANT F344 RAT.
S. R. Bielmeier1, A. S. Murr2, D. S. Best2, J. M. Goldman2, and M. G. Narotsky2
1 Curriculum in Toxicology, Univ. of North Carolina, Chapel Hill, NC, USA
2 Reproductive Toxicology Division, NHEERL, ORD, USEPA, RTP, NC, USA
Sponsor: Robert J. Kavlock
We have reported that BDCM, a drinking water disinfection by-product, causes pregnancy loss, i.e. full-litter resorption, in F344 rats when treated on gestation day (GD) 6-10, encompassing the luteinizing hormone (LH)-dependent period. BDCM-induced pregnancy loss was associated with reductions in serum progesterone (P) and corresponding decreases in LH on GD 10, suggesting BDCM disrupts the maternal hypothalamic-pituitary-gonadal axis. These and other data indicate that BDCM affects the hypothalamus or pituitary gland; however, an effect on luteal responsiveness to LH had not been definitively excluded. To address this data gap, we used an ex vivo approach to assess luteal function. Dams were dosed by gavage on GD 6-9 (plug day = GD 0) at 0 or 100 mg/kg/d (n=11, 12). One hour after the GD-9 dose, rats were sacrificed, blood was collected and corpora lutea (CL) were incubated with or without hCG, an LH agonist, to stimulate P secretion. During the 24 h incubation, media were periodically sampled for hormone analysis by dissociation enhanced lanthanide flouroimmmunoassay (DELFIA?). Luteal responsiveness was unaffected; both groups displayed a 2.4-fold increase in P secretion in response to hCG challenge. Paradoxically, the BDCM-exposed CL showed >2-fold increases in P secretion ex vivo regardless of the presence of hCG; whereas the same animals, i.e., the CL donors, had decreased serum P and LH levels in vivo. It is unclear if this ?rebound' effect reflects the removal of the CL from a possible direct inhibitory influence of BDCM, or a response to the diminished LH stimulation in vivo. Regardless, the lack of effect on luteal responsiveness is further evidence that BDCM-induced pregnancy loss in the rat is due to reduced pituitary LH secretion. 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.