Project Summary The overall goal of this proposal is to investigate the relationship between prenatal androgens and adult cardiometabolic outcomes in a human cohort taking a life-course perspective. Growing evidence suggests that prenatal exposure to androgens may play a role in the programming of metabolic dysfunction and cardiovascular disease in adulthood. Evidence from prenatally androgenized animal models exposed to testosterone in early and late gestation demonstrate several cardiometabolic impairments including hypertension, insulin resistance and adiposity in adult life. Pregnant women with polycystic ovary syndrome (PCOS) have higher testosterone levels during pregnancy and delivery compared to healthy mothers and their offspring tend to develop worse metabolic parameters. Despite evidence from animal studies and patient-specific populations (ie. PCOS), data linking prenatal androgens to adult health outcomes in the general human population has not been well studied. The issue of developmental androgenization is of clinical relevance for investigation because of increasing human exposure to endocrine-disrupting environmental factors that interact with androgen receptor signaling. We propose a study in which: 1) we will relate maternal prenatal androgen levels to offspring early childhood indicators of growth (from birth to age 7), and 2) test their impact on predicting cardiometabolic risk in adulthood 45 years later. The proposed study, in addition to advancing our understanding of early programming effects of androgens on cardiovascular markers, can help identify biomarkers for human disease, potential therapeutic targets and early periods for intervention.

PROJECT NARRATIVE There is considerable data linking early life factors to the development of cardiovascular disease and mortality in adulthood. Growing evidence suggests that prenatal exposure to androgens could be a source of fetal programming leading to the development of cardiovascular and metabolic diseases in later adult life. Although numerous prenatally androgenized animal models have demonstrated cardiometabolic impairments in adulthood, data linking prenatal androgen exposure to long-term adult cardiovascular risk outcomes in the general human population has not been well studied. Using a unique human birth cohort, this proposal will take a life-course perspective to investigate the relationship between prenatal maternal androgens to offspring early childhood indicators of growth and test their impact on predicting cardiometabolic risk in adulthood. The information obtained from this study will provide novel and unique information highlighting a potential mechanism for adverse cardiometabolic outcomes as a consequence of prenatal androgen exposure.