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Toxicology |
Program in Toxicology,3 Department of Epidemiology and Preventive Medicine
and
Department of Physiology,4 University of Maryland, Baltimore, Maryland 21201
Department of Physiology,5 University of Arizona, Tucson, Arizona 85724
Methoxychlor (MXC) is an organochlorine pesticide that increases the rate of ovarian atresia. To date, little is known about the mechanism by which MXC induces atresia. Because Bcl-2 (an antiapoptotic factor), Bax (a proapoptotic factor), gonadotropins, and estradiol are important regulators of atresia in the ovary, the purpose of this study was first to examine whether MXC-induced atresia occurred through alterations in Bcl-2 or Bax, and second, to examine the effect of MXC on gonadotropins, estradiol, and their receptors. CD-1 mice were dosed with 8–64 mg kg–1 day–1 MXC or vehicle (sesame oil). Ovaries were subjected to analysis of antral follicle numbers, Bcl-2, Bax, estrogen receptor, and follicle-stimulating hormone receptor levels. Blood was used to measure gonadotropins and estradiol. In some experiments, mice that overexpressed Bcl-2 or mice that were deficient in Bax were dosed with MXC or vehicle and their ovaries were analyzed for atresia. MXC caused a dose-dependent increase in the percentage of atretic antral follicles compared with controls at the 32 and 64 mg kg–1 day–1 doses of MXC. MXC treatment did not result in changes in Bcl-2 levels, but it did result in an increase in Bax levels in antral follicles. MXC treatment did not affect gonadotropin or estradiol levels, nor did it affect the levels of follicle-stimulating hormone or estrogen receptors. Mice that overexpressed Bcl-2 or mice that were deficient in Bax were protected from MXC-induced atresia. These data suggest that MXC induces atresia through direct effects on the Bax and Bcl-2 signaling pathways in the ovary.
2 Correspondence: Jodi A. Flaws, Department of Epidemiology and Preventive Medicine, 660 West Redwood Street, Baltimore, MD 21210-1596. FAX: 410 706 1503; jflaws{at}epi.umaryland.edu
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