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EFFECT OF AN ACUTE EXPOSURE TO MOLINATE ON OVULATION IN THE LONG-EVANS HOODED RAT
Citation:
Stoker, T E., D. L. Guidici, S C. Jeffay, W. K. McElroy, S P. Darney, AND R L. Cooper. EFFECT OF AN ACUTE EXPOSURE TO MOLINATE ON OVULATION IN THE LONG-EVANS HOODED RAT. Presented at Society of Toxicology, Nashville, TN, March 17-21, 2002.
Description:
EFFECT OF AN ACUTE EXPOSURE TO MOLINATE ON OVULATION IN THE LONG-EVANS HOODED RAT. T E Stoker, D L Guidici, S C Jeffay, W K McElroy, S D Perreault and R L Cooper. Reproductive Toxicology Division, NHEERL, ORD, US EPA, RTP, NC. Sponsor: RJ Kavlock.
Molinate, a thiocarbamate herbicide used on rice, has been shown previously to impair reproductive capability in the male rat. In a two-generation study, molinate exposure to female rats resulted in decreased litter size, ovarian histopathological abnormalities and a slight delay in vaginal opening in the F1 pups. However, published data is lacking on the effects of acute exposure to molinate in the female. Based on reported esterase inhibition by molinate and our previous observations with related dithiocarbamate compounds, we hypothesized that a single exposure to molinate during the critical window for the neural trigger of ovulation on the day of vaginal proestrus would alter the timing of ovulation by blocking the surge of luteinizing hormone (LH). Cycling females gavaged with 0, 25 or 50 mg/kg molinate in corn oil at 1300h on vaginal proestrus were examined for ovulation and oocyte number 24 or 48 h later. All control females ovulated at 24 h. Molinate at 25 mg/kg delayed ovulation for 24 h in 43% of the females, while 50 mg/kg delayed ovulation in 85% of the females. The number of ova present in the delayed females was not different from controls. To examine the effect of molinate on LH secretion, ovariectomized rats were implanted with physiological levels of estradiol and the concentration of the estrogen-induced LH secretion determined in serial tail bleeds at 0, 2, 4 or 6 h after a single oral exposure at 1300 h. 25 mg/kg molinate caused a significant suppression of the LH in 67% of the rats (4 h mean = 0.566 ? 0.1 ng/ml vs 3.560 ? 0.7 ng/ml in controls). 50 mg/kg molinate suppressed the LH surge in 83.3 % of the rats (4 h mean = 0.347 ? 0.1 ng/ml). In a second study, ovariectomized/estradiol-implanted rats were decapitated at 0, 1, 3 and 6 h after exposure at 1300 h. 50 mg/kg significantly suppressed the LH surge in 75% of the females, while 25 mg/kg suppressed the LH surge in 50% of the females. These results indicate that molinate is able to delay ovulation by suppressing the LH surge on the day of proestrus and that the brain and/or pituitary are target sites for this pesticide. These effects could explain in part the effects observed in previously published chronic studies with molinate in the female rat. Because delayed ovulation can result in altered pregnancy outcome and reduced litter size, it will be important to determine the precise CNS/pituitary mechanism involved in this effect.
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