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BOR - Papers in Press, published online ahead of print June 23, 2004.
Biol Reprod 2004, 10.1095/biolreprod.104.033035
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Submitted June 9, 2004
Returned for revision June 10, 2004
Accepted June 10, 2004

Ovary


Direct Effects of Leptin on Mouse Reproductive Function: Regulation of Follicular, Oocyte and Embryo Development

Jason E. Swain , Rodney L. Dunn , Daniel McConnell , Janis Gonzalez-Martinez , and Gary D. Smith *

* To whom correspondence should be addressed. E-mail: smithgd{at}umich.edu.

Abstract
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 production/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 (GVI) 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 to 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 24h 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.

Key words: Embryo • Follicle • Leptin • Oocyte development • Steroid hormones


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