The Oregon National Primate Research Center (ONPRC) proposes to establish a U54 Contraceptive Development Research Center that targets the discovery and development of novel contraceptive agents that prevent one or more periovulatory events in adult, female primates during the menstrual cycle. Four research projects and one animal core utilize Old World (macaque) monkeys to generate new information and proof-of-concept regarding potential modalities for preventing oocyte fertilization, and hence fertility, in women. Project I, """"""""Control of Oocyte Maturation"""""""", will address the hypothesis that novel follicle cell- and oocyte-derived proteins control nuclear and cytoplasmic maturation of the oocyte, and can be exploited to prevent timely egg maturation and hence fertility during the menstrual cycle. Project II, """"""""Control of Cumulus- Oocyte Expansion"""""""", will analyze the granulosa/cumulus cell- and oocyte-derived proteins controlling cumulus-oocyte expansion (C-OE) and test whether specific antagonists disrupt C-OE and hence egg release and fertility in female monkeys. Project III, """"""""Control of Follicle Rupture"""""""", explores the unique proteases expressed in the periovulatory follicle in primates, and whether their inhibition will prevent ovulation and hence egg release and fertility during the menstrual cycle. Project IV, """"""""Control of Gamete Transport and Fertilization"""""""", tests the hypothesis that estrogen action is essential for normal oviductal and cervical function, such that a selective estrogen receptor modulator (SERM) will disrupt oocyte and sperm transport within the reproductive tract, and hence prevent fertilization and fertility in macaques. Whereas basic discovery and elucidation of drug action will be pursued in each Project, promising agents will be tested in the Nonhuman Primate Contraceptive Core for contraceptive efficacy and reversibility, using small groups (10 females to 1-2 males) of macaques in controlled trials. The Administrative Core will foster intra- and inter-center cooperation in contraceptive research, and liaison with the NICHD Project Officer. The U54 CDRC will synergize with existing excellence in reproductive research at ONPRC and the Oregon Health &Science University (OHSU), including several available research service cores and existing ties with the pharmaceutical industry, to promote translational research of direct relevance to testing and formulating novel contraceptives in women.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Specialized Center--Cooperative Agreements (U54)
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Special Emphasis Panel (ZHD1-DSR-A (14))
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Lee, Min S
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Oregon Health and Science University
Schools of Medicine
United States
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Slayden, Ov D; Lee, Dong Ock; Yao, Shan et al. (2016) Polidocanol induced tubal occlusion in nonhuman primates: immunohistochemical detection of collagen I-V. Contraception 94:521-526
Hanna, Carol B; Yao, Shan; Ramsey, Cathy M et al. (2015) Phosphodiesterase 3 (PDE3) inhibition with cilostazol does not block in vivo oocyte maturation in rhesus macaques (Macaca mulatta). Contraception 91:418-22
Jensen, Jeffrey T; Hanna, Carol; Yao, Shan et al. (2015) Characterization of tubal occlusion after transcervical polidocanol foam (PF) infusion in baboons. Contraception 92:96-102
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Edelman, Alison B; Jensen, Jeffrey T; Doom, Carmen et al. (2013) Impact of the prostaglandin synthase-2 inhibitor celecoxib on ovulation and luteal events in women. Contraception 87:352-7
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Stouffer, Richard L; Bishop, Cecily V; Bogan, Randy L et al. (2013) Endocrine and local control of the primate corpus luteum. Reprod Biol 13:259-71
Micks, Elizabeth; Shekell, Taylor; Stanley, Jessica et al. (2012) Medical termination of pregnancy in cynomolgus macaques. J Med Primatol 41:394-402
Keator, Christopher S; Mah, Kuni; Slayden, Ov D (2012) Alterations in progesterone receptor membrane component 2 (PGRMC2) in the endometrium of macaques afflicted with advanced endometriosis. Mol Hum Reprod 18:308-19
Hanna, Carol B; Yao, Shan; Wu, Xuemei et al. (2012) Identification of phosphodiesterase 9A as a cyclic guanosine monophosphate-specific phosphodiesterase in germinal vesicle oocytes: a proposed role in the resumption of meiosis. Fertil Steril 98:487-95.e1

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