Methoxychlor Disrupts Uterine Hoxa10 Gene Expression

Methoxychlor (MXC) is a pesticide that has adverse effects on reproductive capability inmice.MXCand itsmetabolites bind the estrogen receptor and function as endocrine disruptors. MXCdiminishes the uterine decidual cell response, necessary for the support of pregnancy.Hoxa10 is an estrogen-regulated gene that is an essential mediator of the decidual response and necessary for pregnancy. Here we demonstrate that a mechanism by which MXC disrupts uterine function is by suppressing Hoxa10 expression. MXC treatment of mice pro-duced a mild uterotropic response as measured by increased uterine weight and epithelial height. MXC treatment of uter-ine Ishikawa cells in vitro induced Hoxa10 expression. Estro-gen receptor (ER) binding to the HOXA10 estrogen response element (ERE)waspromotedby treatmentwithestradiol (E2); however, MXC disrupted E2/ER/ERE complex formation an