PARENT SESSION
SLIDE SESSION 6: REPRODUCTIVE TOXICOLOGY IN THE MALE AND FEMALE
Chairs: Janice Bailey, Rao Veeramachaneni, Christina Borgeest (Trainee)
Univ Ottawa-Monpetit 203
2:30 PM-4:30 PM
39
ESTROGENIC PESTICIDES MAY CAUSE FOLLICULAR ATRESIA, ALTERED ESTROGEN RECEPTOR ALPHA (ER
) LEVELS AND PERSISTENT ESTRUS IN THE MOUSE.
Borgeest, Christina1, Hruska, Kathleen2, Flaws, Jodi3, 1 2 3
ABSTRACT- The effects of estrogenic pesticides on the female reproductive system are not well understood. Thus, the purpose of this study was to test the hypothesis that two such pesticides, methoxychlor and kepone, increase ovarian atresia, alter ovarian ER levels and disrupt estrous cyclicity in mice. Methoxychlor was chosen because it is an organochlorine pesticide and suspected endocrine disruptor that is currently used to protect fruits and vegetables from insects. Kepone was chosen because it is a persistent organochlorine pesticide that was widely used before it was banned in 1977, and it is a known ovarian toxicant. To test this hypothesis, we dosed adult CD-1 mice (39 days) five days/week for 10 and 20 days with sesame oil (control), methoxychlor (8mg/kg/d) or kepone (8mg/kg/d). Estrous cyclicity was evaluated daily and ovaries were collected from the mice on diestrus after 10 days of dosing or on the 20th day of dosing. One ovary was processed for histological evaluation and the other was snap frozen for western blot analysis of ER levels. After 20 days of dosing, mice treated with the pesticides had a significantly greater percentage of atretic follicles than controls (control = 42.2± 3.9% atretic follicles, n=6; methoxychlor = 57.4± 3.0% atretic follicles, n=6; kepone = 59.0± 2.9% atretic follicles, n=6; p<0.02). At the 10 day time-point, ovarian ER levels were decreased by approximately 50% in mice treated with kepone, but remained the same in those treated with methoxychlor. Mice dosed with methoxychlor or kepone for 10 days showed relatively normal cyclicity, but after 16 days they went into constant estrus. These data suggest that both methoxychlor and kepone destroy ovarian follicles and that kepone affects ovarian ER levels. These data also suggest that methoxychlor and kepone disrupt estrous cyclicity. Supported by NIH HD 38955 and the Women's Health Research Group at the University of Maryland.
KEY WORDS: methoxychlor, kepone, follicle, atresia