Hyperandrogenemia, Diet and Female Reproductive Health

总结/摘要 俄勒冈州健康与科学大学（OHSU）的俄勒冈州国家灵长类动物研究中心（ONPRC） P50国家生殖和不孕症转化研究中心（NCTRI） 该项目涉及高雄激素血症和肥胖症对女性生殖健康的影响。多年来的进展 01 - 05发现代谢，脂肪组织，卵巢和子宫病变，以及生育力低下， 睾酮和/或西式饮食（WSD）治疗雌性猕猴，从青春期开始至 年轻的成年建议进一步研究，以确定是否：（1）影响变得更加明显， 治疗持续到成年期，以及（2）这些影响至少部分地通过取消治疗而逆转。 ONPRC的三个研究项目使用非人灵长类动物模型，一个项目侧重于特定的 多囊卵巢综合征（PCOS）患者的临床资料项目一，"代谢和 脂肪对高雄激素血症和饮食的反应"是C。罗伯茨角真实而 O.瓦拉莫夫项目二，“卵巢结构-功能：雄激素和饮食的影响”，包括J。 亨内博尔德河Stouffer和S，Chavez。项目III，"雄激素和饮食对子宫胎盘的影响 功能"，涉及博士。Slayden，A.弗里亚斯和L.迈亚特项目四，"雄激素过量导致肥胖 多囊卵巢综合征妇女的功能障碍"，包括一个财团与博士。Dumesic和G. Chazenbalk在 加州大学洛杉矶分校妇产科。项目I-III将由非人灵长类动物（NHP）核心（O。 Slayden，主管）作为封闭资源运行。该核心将保留四个治疗组， 恒河猴（对照组、睾酮或T治疗组、WSD治疗组和T + WSD组）， 包括生育试验然后，将支持测试T和WSD去除效果的程序， 包括另一项生育试验行政核心（Drs. R。Stouffer和J. Hennebold）将指导 国家技术研究所开展活动，促进与其他中心和国家排雷中心官员的互动。外展核心（D。 戈登和M博士Zelinski）将提高公众对生殖健康研究的认识和理解。 关于雄激素和饮食相关因素的作用，无论是个体还是个体，都将积累重要的新信息。 组合，与生育障碍如PCOS的病因学相关。此外，可逆性数据将提供 对新疗法可能疗效的洞察，包括可能限制疗法的表观遗传变化。 据估计，人类不育症的患病率为9%，越来越多的证据表明， 高雄激素血症或肥胖症单独导致生殖功能障碍，且联合收割机组合进一步损害生育力。 然而，雄激素的原因与影响，特别是与生殖功能障碍有关， 争议在灵长类动物和正常体重的PCOS女性中进行的机制研究将区分这些角色 慢性雄激素暴露和饮食，并提供深入了解改善治疗不孕症。

SUMMARY/ABSTRACT The Oregon National Primate Research Center (ONPRC) at the Oregon Health & Science University (OHSU) proposes to renew its P50 National Center for Translational Research in Reproduction and Infertility (NCTRI) that addresses the effects of hyperandrogenemia and obesity on female reproductive health. Progress in years 01-05 identified metabolic, adipose tissue, ovarian and uterine lesions, as well as subfertility, following chronic testosterone and/or a western-style diet (WSD) treatment of female macaques beginning at puberty through young adulthood. Further studies are proposed to determine if: (1) the effects become more pronounced as treatment continues into adulthood, and (2) the effects are, at least in part, reversed by removal of treatment. Three research projects use the nonhuman primate model at ONPRC, and one project focuses on the specific population of normal weight women with polycystic ovary syndrome (PCOS) at UCLA. Project I, “Metabolic and Adipose Responses to Hyperandrogenemia and Diet” is a collaboration between Drs. C. Roberts, C. True and O. Varlamov. Project II, “Ovarian Structure-Function: Influence of Androgen and Diet”, includes Drs. J. Hennebold, R. Stouffer and S, Chavez. Project III, “Effects of Androgen and Diet on Uterine-Placental Function”, involves Drs. O. Slayden, A. Frias and L. Myatt. Project IV, “Androgen Excess Causes Adipogenic Dysfunction in PCOS Women”, incorporates a consortium with Drs. D. Dumesic and G. Chazenbalk in the Department of Ob-Gyn, UCLA. Projects I-III will be supported by a nonhuman primate (NHP) Core (O. Slayden, Supervisor) operating as a closed resource. This Core will maintain four treatment groups of female rhesus monkeys (control, testosterone or T-treated, WSD-treated and T+WSD) for two additional years, including a fertility trial. Then procedures testing the effects of removal of T and WSD will be supported, including another fertility trial. The Administrative Core (Drs. R. Stouffer and J. Hennebold) will direct the NCTRI activities and promote interactions with other centers and NICHD officers. The Outreach Core (D. Gordon and Dr. M. Zelinski) will increase public awareness and understanding of reproductive health research. Important new information will accrue on the actions of androgen and diet-related factors, individually and in combination, relevant to the etiology of fertility disorders, such as PCOS. Also, the reversibility data will provide insight on the possible efficacy of novel treatments, including epigenetic changes that may limit therapies. The estimated prevalence of infertility in the human population is 9%, with mounting evidence that hyperandrogenemia or obesity alone lead to reproductive dysfunction, and combine to further impair fertility. However, the causes versus effects of androgen, particularly as related to reproductive dysfunction, are controversial. Mechanistic studies in primates and normal-weight PCOS women will discern between the roles of chronic androgen exposure and diet, and offer insight into improving therapy for infertility.