Direct effects of leptin on mouse reproductive function: Regulation of follicular, oocyte, and embryo development

Because body condition can affect reproduction, research has focused on the role of leptin, a body condition signal, in regulation of reproductive function. Objectives of this study were to determine if leptin supplementation directly affects 1) ovarian follicle growth and function, 2) oocyte maturation, or 3) preimplantation embryo development. Follicles cultured in the presence of recombinant mouse leptin resulted in a significant decrease in rate of follicle, but not oocyte, growth in a dose-dependent manner, with higher doses of leptin inhibiting growth. Leptin was also found to significantly increase stimulated progesterone, estradiol, and testosterone prod uction/secretion by cultured follicles in a dose-dependent manner, with higher concentrations of leptin significantly increasing steroidogenesis. Culture of fully grown cumulus-enclosed germinal vesicle-intact (GV) mouse oocytes in the presence of increasing concentrations of leptin (0, 12.5, 25, 50, 100 ng/ml) had no effect on germinal vesicle breakdown (GVBD) or development to metaphase II (MII). Similarly, fully grown denuded oocytes showed no difference in GVBD at any concentration of leptin. However, maturation of denuded oocytes with 100 ng/ml leptin resulted in significantly reduced development to MII compared with oocytes matured with 0 or 12.5 ng/ml leptin. Culture of one-cell mouse embryos in increasing concentrations of leptin had no effect on cleavage or blastomere degeneration at 24 h of culture. Exposure of embryos for the first 96 h of development to increasing concentrations of leptin did not significantly affect total or expanded blastocyst development or hatching of blastocysts from zona pellucida. These results indicate leptin directly enhances insulin and gonadotropin-stimulated ovarian steroidogenesis, compromises denuded oocyte maturation, yet has no direct effect on preimplantation embryo development.