This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.The long-range goal of this research is to understand the role of local factors, e.g., bone morphogenetic proteins (BMPs) in controlling ovarian function, particularly follicular development and oocyte maturation in primates. Evidence from rodents suggests that BMPs, notably GDF-9 and BMP-15, have important local actions controlling follicular/granulosa cell differentiation and oocyte development, including expansion of the cumulus-oocyte-complex just prior to ovulation. Preliminary data generated by the NICHD's Specialized Cooperative Centers Program in Reproduction Research at Baylor University (M. Matzuk) and Oregon Health & Science University (R. Stouffer) suggest that the GDF-9/BMP-15-receptor systems are present and active in the primate ovary. Therefore, translational studies are planned: (1) To produce large amounts of purified recombinant human GDF-9 and BMP-15, plus neutralizing antibodies to these proteins, for in vitro and in vivo studies in primates; and (2) To examine the effects of exogenous and endogenous GDF-9 and BMP-15 on mural granulosa cells and cumulus-oocyte-complexes (COCs) from nonhuman primates and women. Dr. Matzuk's group will perform experiments in Aim No. 1, as well as experiments with human cells in Aim No. 2. Dr. Stouffer's group will perform experiments using rhesus monkey cells in Aim No. 2: (a) macaque granulosa cells from preovulatory follicles will be cultured in the presence and absence of BMPs, and RNA preparations shipped to Baylor for analysis of the transcriptomes by microarrays; (b) macaque cumulus-oocyte-complexes will be incubated in the presence or absence of gonadotropin hormones, BMPs and/or BMP antibodies, and cumulus expansion quantitated by image analysis.
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