The Nonhuman Primate Contraceptive Core (NPC Core) provides services and coordination of animal usage for U54 Contraceptive Center investigators with approved projects. The NPC Core maintains a pool of cynomolgus macaque females and males in the Division of Animal Resources (DAR), ONPRC, available for contraceptive (mating) trials;coordinates and performs studies on potential contraceptive agents;confirms menstruation and ensures mating has occurred by taking vaginal swabs;performs ultrasounds to monitor for pregnancies;and obtains blood samples for hormone assays, pharmacokinetic studies and metabolic profiles. The Core acclimates the females to a small group (harem) housing situation (10 females to one male) wherein they can be separated for daily vaginal checks, dosing, blood sampling and ultrasound analyses. In addition, the NPC Core trains investigators in established protocols and disseminates information on emerging approaches. The NPC Core represents an efficient use of animals and personnel, and provides assistance that is prohibitively expensive to establish in individual investigator's laboratories. The final stage in the strategy to discover novel agents for female fertility regulation will be to evaluate the efficacy of ovary/reproductive tract-specific agents as reversible or irreversible contraceptive agents in a nonhuman primate model. Cost-effective, experimental contraceptive trials of these inhibitors for each individual project in the U54 will be performed in the NPC Core with the following specific aims:
Specific Aim 1 : demonstrate a contraceptive effect of chronic (6 month) administration of the inhibitor in a breeding colony of macaques exhibiting natural menstrual cycles.
Specific Aim 2 : document if the contraceptive effect is reversible following discontinuation for a 6 month interval Data from these translational experiments conducted in the NPC Core will increase confidence in the feasibility of considering a similar regimen of inhibitor(s) for clinical use as a contraceptive in women.
The NPC Core is uniquely poised to drive cost-effective, proof-of-concept studies in nonhuman primates that can be readily translated to test novel ovai7/reproductive tract-specific agents as reversible or irreversible contraceptives in women. Data from translational studies conducted in the NPC Core will increase confidence in the feasibility of considering a similar regimen of these agents for clinical use as contraceptives in women.
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|Xu, Fuhua; Stouffer, Richard L; Muller, Jorg et al. (2011) Dynamics of the transcriptome in the primate ovulatory follicle. Mol Hum Reprod 17:152-65|
|Peluffo, Marina C; Murphy, Melinda J; Baughman, Serena Talcott et al. (2011) Systematic analysis of protease gene expression in the rhesus macaque ovulatory follicle: metalloproteinase involvement in follicle rupture. Endocrinology 152:3963-74|
|Peluffo, Marina C; Barrett, Susan L; Stouffer, Richard L et al. (2010) Cumulus-oocyte complexes from small antral follicles during the early follicular phase of menstrual cycles in rhesus monkeys yield oocytes that reinitiate meiosis and fertilize in vitro. Biol Reprod 83:525-32|
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