Hyperandrogenemia, Diet and Female Reproductive Health

高雄激素血症、饮食和女性生殖健康

• 批准号: 9908126
• 负责人: Jon D Hennebold
• 金额: $ 173.56万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-04-01 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9908126
• 关键词: Address; Adipose tissue; Adult; Aftercare; Age; Androgens; Animals; Awareness; Blood; Center for Translational Science Activities; Characteristics; Chronic; Collaborations; Collection; Data; Defect; Development; Development Plans; Diet; Disease; Endometrial; Epigenetic Process; Etiology; Excision; Exposure to; Fatty acid glycerol esters; Female; Female Adolescents; Fertility; Fertility Disorders; Fetus; Follicular Fluid; Functional disorder; Gene Expression; Genetic; Health Sciences; High Fat Diet; Hormones; Human; Impairment; Implant; In Vitro; Individual; Infertility; Investigation; Knowledge; Lead; Macaca; Macaca mulatta; Measures; Menarche; Metabolic; Metabolism; Modeling; Molecular; Molecular Analysis; Monkeys; National Institute of Child Health and Human Development; Obesity; Oregon; Ovarian; Partner in relationship; Pathologic; Performance; Periodicity; Phenotype; Pilot Projects; Polycystic Ovary Syndrome; Population; Pre-implantation Embryo Development; Pregnancy; Pregnancy loss; Prevalence; Prevention; Primates; Procedures; Puberty; Reducing diet; Reproduction; Reproductive Health; Reproductive system; Research; Research Personnel; Research Project Grants; Research Support; Resources; Retirement; Risk; Role; Science; Series; Sterols; Structure; Syndrome; Testing; Testosterone; Thinness; Tissue Sample; Tissues; Translational Research; Ultrasonography; Universities; Uterine Lesion; Uterus; Vision; Weight; Withholding Treatment; Woman; Women' s Group; Women' s Health; base; clinically relevant; cohort; fetal; granulosa cell; implantation; improved; in utero; in vivo; insight; member; metabolic abnormality assessment; non-invasive imaging; nonhuman primate; novel; obesogenic; oocyte quality; outreach; reproductive; reproductive function; response; stem cells; subfertility; sugar; time-to-pregnancy; treatment effect; treatment group; young adult

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.

摘要/摘要 俄勒冈健康与科学大学 (OHSU) 的俄勒冈国家灵长类动物研究中心 (ONPRC) 提议更新其 P50 国家生殖与不孕转化研究中心 (NCTRI) 解决高雄激素血症和肥胖对女性生殖健康的影响多年来取得了进展。 01-05 发现慢性病后的代谢、脂肪组织、卵巢和子宫病变以及生育力低下 从青春期开始对雌性猕猴进行睾酮和/或西式饮食（WSD）治疗 建议进一步研究以确定：（1）随着年龄的增长，影响是否会变得更加明显。 治疗持续到成年，并且（2）通过取消治疗，效果至少部分逆转。 ONPRC 的三个研究项目使用非人类灵长类动物模型，其中一个项目专注于特定的 加州大学洛杉矶分校项目 I 中患有多囊卵巢综合征 (PCOS) 的正常体重女性群体，“代谢和卵巢功能障碍”。 《脂肪对高雄激素血症和饮食的反应》是 C. Roberts、C. True 博士和 O. Varlamov，项目 II，“卵巢结构-功能：雄激素和饮食的影响”，包括 J. Hennebold、R. 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 O. Slayden、A. Frias 和 L. Myatt 博士，项目 IV，“雄激素过多导致脂肪形成”。 多囊卵巢综合症女性的功能障碍”，由 D. Dumesic 和 G. Chazenbalk 博士组成的联盟。 加州大学洛杉矶分校妇产科项目 I-III 将得到非人类灵长类动物 (NHP) 核心 (O. Slayden，主管）作为封闭资源运作，将维持四个女性治疗组。 恒河猴（对照、睾酮或 T 治疗、WSD 治疗和 T+WSD）另外两年， 然后将支持测试去除 T 和 WSD 效果的程序， 行政核心（R. Stouffer 博士和 J. Hennebold 博士）将指导另一项生育试验。 NCTRI 活动并促进与其他中心和 NICHD 官员的互动（D. Gordon 和 M. Zelinski 博士）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单独作用和整体作用的重要新信息将会产生。 组合，与生育障碍的病因相关，例如多囊卵巢综合症。此外，还将提供可逆性数据。 了解新疗法的可能功效，包括可能限制疗法的表观遗传变化。 据估计，人群中不孕不育的患病率为 9%，越来越多的证据表明 高雄激素血症或肥胖单独导致生殖功能障碍，并结合进一步损害生育能力。 然而，雄激素的原因与影响，特别是与生殖功能障碍相关的因素，尚不清楚。 对灵长类动物和正常体重的多囊卵巢综合症女性的机制研究将区分这些角色。 慢性雄激素暴露和饮食的影响，并为改善不孕症治疗提供见解。