Methoxychlor-induced atresia in the mouse involves Bcl-2 family members, but not gonadotropins or estradiol

Christina Borgeest, Kimberly P. Miller, Rupesh Gupta, Chuck Greenfeld, Kathleen S. Hruska, Patricia Hoyer, Jodi A. Flaws

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1828-1835
Number of pages8
JournalBiology of reproduction
Volume70
Issue number6
DOIs
StatePublished - Jun 2004
Externally publishedYes

Keywords

  • Apoptosis
  • Environment
  • Follicle
  • Ovary
  • Toxicology

ASJC Scopus subject areas

  • Cell Biology

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