The proposed work will investigate the mechanism by which the aryl hydrocarbon receptor (AhR) affects ovarian folliculogenesis. Despite having a role in mediating toxicity, little is known about this receptor. So far, AhR-deficient mice (AhRKO mice) have been shown to have a decrease in the numbers of ovarian antral follicles compared to wild-type (WT) mice. Studies have also shown that this decrease is due to delayed growth to the antral stage and not follicle death. The exact mechanism by which the AhR affects follicular growth is still unknown. One possible mechanism for this delayed follicular growth may be that estradiol (E2) levels are altered in AhRKO mice compared to WT mice. Since estrogens are required for normal growth and maturation of ovarian follicles, our hypothesis is that the AhR affects folliculogenesis via mechanisms involving estrogen steroidogenesis. To test this hypothesis, the following specific aims will be completed: 1) Characterize and compare E2 and its receptors, estrogen receptor a(ERa) and estrogen receptor b(ERb) in AhRKO and WT mice; 2) Characterize and compare Cytochrome P450 metabolizing enzymes and precursor hormones in AhRKO and WT mice required for estrogen synthesis; and 3) Determine if the administration of E2 will rescue the AhRKO mouse phenotype. The proposed study will further our understanding of mechanisms attributing to the reproductive abnormalities of these AhRKO mice; which may ultimately lead to improvements on fertility.
|Hernandez-Ochoa, Isabel; Barnett-Ringgold, Kimberly R; Dehlinger, Stacey L et al. (2010) The ability of the aryl hydrocarbon receptor to regulate ovarian follicle growth and estradiol biosynthesis in mice depends on stage of sexual maturity. Biol Reprod 83:698-706
|Barnett, Kimberly R; Tomic, Dragana; Gupta, Rupesh K et al. (2007) The aryl hydrocarbon receptor is required for normal gonadotropin responsiveness in the mouse ovary. Toxicol Appl Pharmacol 223:66-72
|Barnett, Kimberly R; Tomic, Dragana; Gupta, Rupesh K et al. (2007) The aryl hydrocarbon receptor affects mouse ovarian follicle growth via mechanisms involving estradiol regulation and responsiveness. Biol Reprod 76:1062-70
|Barnett, K R; Schilling, C; Greenfeld, C R et al. (2006) Ovarian follicle development and transgenic mouse models. Hum Reprod Update 12:537-55