You are here:
DEVELOPMENTAL EFFECTS OF DISINFECTANT BY-PRODUCTS BROMOFORM, BROMODICHLOROMETHANE, BROMODICHLOROACETIC ACID, AND BROMOCHLOROACETIC ACID IN MICE
Citation:
Narotsky, M G., D S. Best, E H. Rogers, AND E S. Hunter III. DEVELOPMENTAL EFFECTS OF DISINFECTANT BY-PRODUCTS BROMOFORM, BROMODICHLOROMETHANE, BROMODICHLOROACETIC ACID, AND BROMOCHLOROACETIC ACID IN MICE. Presented at Teratology Society Meeting, Montreal, Quebec, Canada, June 23-28, 2001.
Description:
PREGNANCY LOSS CAUSED BY ATRAZINE IN F344 RATS:
EFFECTS ON SERUM PROGESTERONE LEVELS.
M.G. Narotsky1, D.S. Best1, S.R. Bielmeier1 and R.L. Cooper1.
1Endocrinology Branch, US Environmental Protection Agency, Research
Triangle Park, NC, United States
Previously we reported that exposure to atrazine, a widely used herbicide,
disrupted ovarian cycling in rats. We also showed that atrazine can inhibit the
ovulatory surge and pulsatile release of luteinizing hormone (LH). More recently,
we demonstrated that atrazine exposure on gestation days (GD) 6-10, roughly
coinciding with the LH-dependent period of pregnancy (GD 7-10), can cause
pregnancy loss (i.e., full-litter resorption) in rats. During the LH-dependent
period, LH is required to maintain pregnancy by stimulating luteal secretion of
progesterone. As part of our efforts to confirm the hypothesis that
atrazine-induced pregnancy loss is LH mediated, we evaluated atrazine's effects
on gestational progesterone levels. F344 rats were treated by gavage with 0,
100, or 200 mg atrazine/kg/d 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 levels were determined by ELISA. Dams were allowed to deliver
and their litters were examined postnatally. For females that did not deliver,
pregnancy loss was confirmed by staining uterine resorption sites with 10%
ammonium sulfide. All 7 control dams successfully maintained their pregnancies
whereas 8 of 10 dams at 100 mg/kg and 6 of 9 dams at 200 mg/kg had
pregnancy loss. Treated dams, particularly with pregnancy loss, had significantly
reduced serum progesterone levels on GD 11. For control, 100-mg/kg, and
200-mg/kg dams with live litters, mean (? SE) GD-11 values were 170 ? 20, 98
? 23, and 78 ? 13 ng/ml, respectively; whereas 100-mg/kg and 200-mg/kg dams
with pregnancy loss had respective values of 36 ? 6 and 64 ? 18 ng/ml.
Pregnancy loss was associated with progressively reduced progesterone levels
resulting in marked reductions by GD 11. Whereas all control values were >95
ng/ml, increasing numbers of dams with pregnancy loss had moderately reduced
values (<95 ng/ml) on GD 9-10, and markedly reduced values (<50 ng/ml) on
GD 10-11. Although a direct ovarian effect remains possible, these findings are
consistent with reduced secretion of LH, and may reflect an LH-mediated
mechanism. [This abstract does not necessarily reflect EPA policy.]