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GENE EXPRESSION IN THE PRIMATE OVULATORY FOLLICLE

$3,099P51FY2011RRNIH

Oregon Health & Science University, Portland OR

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Abstract

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. In mammalian species, the midcycle surge of gonadotropin hormone (notably luteinizing hormone, LH) secreted by the pituitary gland, initiates a cascade of events in the ovary leading to ovulation of the mature follicle (i.e., rupture of the follicle wall and release of its enclosed oocyte),.. As part of the process, the gonadotropin surge acts on the preovulatory follicle to elicit cumulus-oocyte maturation, including reinitiation of meiosis in the oocyte and expansion of the surrounding cumulus cells, thereby producing a fertilizable egg that can be released from the follicle at ovulation. Rodent studies suggest that prostaglandin (PG) synthesis and local PGE2-receptor (via PGER2 not R1) action is critical for periovulatory events, including cumulus-oocyte expansion (C-OE), and fertility. Studies performed in the Stouffer laboratory demonstrated significant increases in mRNA levels for the enzymes involved in PGE synthesis, as well as PGER2, in the periovulatory follicle of rhesus macaques. Therefore, further studies were designed to evaluate whether a PGE2 antagonist, compared to vehicle control: (1) altered timely ovulation during the natural menstrual cycle, and (2) blocked C-OE in the periovulatory follicle, in rhesus monkeys. In-vivo and in vitro studies suggest that PGE2-receptor signaling promotes C-OE in primates, and provided the rationale for a new project to determine if a PGE2 antagonist was an effective, reversible contraceptive in adult, cycling monkeys.

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GENE EXPRESSION IN THE PRIMATE OVULATORY FOLLICLE · GrantIndex