DETERMINING PCOS-LIKE TRAITS IN MACAQUES AND NEWBORN HUMAN INFANTS

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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. DESCRIPTION (provided by applicant): Polycystic ovary syndrome (PCOS) is the most prevalent women's endocrinopathy conferring increased lifetime risk of infertility, type 2 diabetes, cardiovascular disease and endometrial cancer. The etiology of PCOS remains unknown due, in part, to the lack of (1) a naturally-occurring animal model and (2) a pediatric phenotype. We propose to initiate a 1-year pilot study to address both issues by capitalizing on our identification of nonhuman primate PCOS phenotypes and our potential ability to detect a pediatric antecedent to PCOS in human infants. Aims 1 and 2 will employ reproductive and somatometric assessments to identify spontaneously occurring androgen excess, diminished fertility/fecundity, polycystic ovaries and elevated anti-mullerian hormone (hallmarks of PCOS) in adult female cynomolgus and rhesus macaques permitting initial heritability analyses in the latter. Aim 3 will translate the hyperandrogenic phenotype found in newborn infant androgeri-exposed female monkeys into identification of human infant giris with risk of future PCOS, and will engage mass spectrometry techniques recently developed by the Wisconsin CTSA Assay Services to determine fetal exposure to androgen excess in a lock of human infant head hair, thus providing the first confirmation of our proposed developmental origins for PCOS. The meeting organized in Aim 4 will evaluate study outcomes and devise follow-up strategies to identify the basis for spontaneous PCOS in primates and altered trajectory of pre-pubertal endocrine and metabolic development that precedes adult PCOS in women. The overall aim is to translate Primate Center and CTSA expertise and resources into novel therapeutic or lifestyle interventions to prevent PCOS in adulthood. All four Aims proposed in this Revision Award submission will strengthen the 5-year plans for PCOS research in both the Regenerative Medicine & Reproduction and Aging & Metabolism Area research groups at the Wisconsin National Primate Research Center (WNPRC), while Aims 1-3 will expand Specific Aims 3 and 4 of WNPRC Assay Services in the P51 parent grant with regard to advances in steroid hormone determination. PUBLIC HEALTH RELEVANCE (provided by applicant): Identification of polycystic ovary syndrome (PCOS) in nonhuman primates will provide models for determining the origins ofthis prevalent women's health disorder resulting in infertility, type 2 diabetes and obesity. Determining testosterone in head hair will permit translation of this noninvasive technique into clinical identification of newborn human female infants at risk for PCOS.