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与 从生命过程的角度看成人心脏代谢结果。越来越多的证据 表明产前暴露于雄激素可能在代谢的编程中发挥作用， 功能障碍和心血管疾病。来自产前雄激素化动物的证据 在妊娠早期和晚期暴露于睾酮的模型显示了几种心脏代谢 成年后的高血压、胰岛素抵抗和肥胖症等疾病。孕妇 多囊卵巢综合征（PCOS）患者在怀孕期间的睾酮水平较高， 分娩与健康母亲相比，其后代往往发展更差的代谢 参数尽管动物研究和患者特定人群（即，PCOS），数据 在一般人群中，将产前雄激素与成人健康结果联系起来， 好好研究。发育雄激素化的问题是临床相关的调查 由于人类越来越多地暴露于内分泌干扰的环境因素， 雄激素受体信号传导。我们提出了一项研究，其中：1）我们将涉及产妇产前 雄激素水平对后代早期儿童生长指标（从出生到7岁）的影响，以及2）测试他们的 对预测45年后成人心脏代谢风险的影响。此外，拟议的研究 促进我们对雄激素对心血管疾病的早期编程作用的理解， 标记物，可以帮助识别人类疾病的生物标志物，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.