Pregnancy loss in the rat caused by bromodichloromethane.
Bromodichloromethane (BDCM), a trihalomethane, is a by-product of the chlorination of drinking water. In a recent epidemiological study, consumption of BDCM was associated with an increased risk of spontaneous abortion in pregnant women. We have previously shown that BDCM causes pregnancy loss, i.e., full-litter resorption (FLR), in the F344 rat. The mode of action was investigated, with three main findings. First, there was a dramatic difference in sensitivity between F344 and Sprague-Dawley (SD) rat strains. Following aqueous gavage treatment on gestational days (GD) 6-10, F344 rats had a 62% incidence of FLR at 75 mg/kg/day, whereas all SD rats maintained their litters. Second, the critical period encompassed the luteinizing hormone (LH)-dependent period of pregnancy. Rats treated on GD 6-10 at 75 mg/kg/day had a 75% incidence of FLR, but rats treated on GD 11-15 at 75 or 100 mg/kg/day were unaffected. Third, 24 h after a single dose, all dams with FLR had markedly reduced serum progesterone levels; however, LH levels were unaffected. The high FLR rate during the LH-dependent period, the lack of response thereafter, and the reduced progesterone levels without an associated reduction in LH levels suggests that BDCM disrupts luteal responsiveness to LH.
Bielmeier
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Curriculum of Toxicology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA. bielmeier.susan@epa.gov
Best
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Guidici
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Narotsky
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D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002273:Carcinogens / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D020964:Embryo Loss / Q000139:chemically induced*; D005260:Female; D005327:Fetal Resorption / Q000139:chemically induced*; D007986:Luteinizing Hormone / Q000097:blood; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000097:blood / Q000187:drug effects*; D011374:Progesterone / Q000097:blood; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D013045:Species Specificity; D022882:Trihalomethanes / Q000633:toxicity*
D002273:Carcinogens; D022882:Trihalomethanes; D011374:Progesterone; C025191:bromodichloromethane; D007986:Luteinizing Hormone