PARACRINE DYSREGULATION OF OOCYTE COMPETENCE IN POLYCYSTIC OVARY SYNDROME

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. To further develop the prenatally androgenized (PA) female rhesus monkey as a model for PCOS. Polycystic ovary syndrome (PCOS) in women is characterized by anovulation, LH hypersecretion, hyperandrogenism and insulin resistance. As the most common female endocrine pathology, affecting 4-7% of reproductive-aged women, and as a frequent cause of infertility, accounting for 75% of anovulation, PCOS has staggering adverse physiological, psychological and financial consequences for women's reproductive health. During gonadotropin stimulation for in vitro fertilization (IVF), PCOS women experience decreased fecundity and increased pregnancy loss. Since experimental investigation of egg and embryo development in humans is limited by ethical constraints, we have developed the prenatally androgenized (PA) female rhesus monkey as a model for PCOS. In an on-going study, PA female monkeys undergoing follicle stimulating hormone (FSH) therapy for IVF exhibit androgen excess in the follicular fluid of stimulated follicles, typical of PCOS women undergoing similar fertility treatment, while also requiring more FSH treatment to produce mature oocytes compared to normal female monkeys. Follicular androgen excess may perturb the development of mature oocytes, and the increased requirement for FSH treatment suggests reduced ovarian reserve of follicles. Both abnormalities may compromise oocyte maturation. The long-term objectives of this proposal are to define molecular markers of egg developmental competence that enhance IVF pregnancy outcome by improving embryo development, while minimizing pregnancy loss in women with PCOS. This research used WNPRC Animal Services, Assay Services and Central Protocol Implementation unit. Funding ended Aug. 31, 2007.