Prenatal Androgens and Cardiometabolic Risk in Adulthood

项目摘要 这项建议的总体目标是调查产前雄激素和 从生命过程的角度观察人类队列中成人心脏代谢结果。越来越多的证据 提示孕期接触雄激素可能在代谢规划中发挥作用 成年期的功能障碍和心血管疾病。产前雄激素化动物的证据 妊娠早期和晚期暴露于睾酮的模型显示多种心脏代谢 成人生活中的损害包括高血压、胰岛素抵抗和肥胖症。怀孕妇女 患有多囊卵巢综合征(PCOS)的患者在怀孕期间睾酮水平较高， 分娩与健康的母亲及其子女相比，往往会发展为更差的代谢 参数。尽管有来自动物研究和特定患者群体的证据(即。PCOS)、数据 在一般人群中，产前雄激素与成人健康结果之间的联系尚未得到证实 研究得很好。发育性雄激素化的问题具有临床意义 因为人类越来越多地接触到相互作用的内分泌干扰环境因素 与雄激素受体信号有关。我们提出了一项研究，在该研究中：1)我们将与母亲产前有关 雄激素水平对后代早期儿童生长的指标(从出生到7岁)，和2)测试他们的 45年后对成年后心脏代谢风险预测的影响。拟议的研究，此外 以增进我们对雄激素对心血管的早期编程效应的理解 标记物，可以帮助识别人类疾病的生物标记物，潜在的治疗靶点和早期 干预期。

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.