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俄勒冈国家灵长类研究中心 建议更新其P50国家生殖和不孕症翻译研究中心(NCTRI) 这解决了高雄激素血症和肥胖对女性生殖健康的影响。按年计算的进度 01-05确定了代谢、脂肪组织、卵巢和子宫损害以及不育症， 从青春期开始对雌性猕猴进行睾酮和/或西式饮食(WSD)治疗 青壮年。建议进行进一步的研究，以确定：(1)影响是否会变得更加明显，因为 治疗持续到成年，以及(2)这种影响至少部分地被取消治疗所逆转。 ONPRC的三个研究项目使用了非人类灵长类动物模型，一个项目专注于特定的 加州大学洛杉矶分校患有多囊卵巢综合征(PCOS)的正常体重妇女的人口。项目一，“新陈代谢和 高雄激素血症与饮食的脂肪反应“是C.Roberts博士、C.True博士和 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，R.斯托弗和S，查韦斯。项目III，“雄激素和饮食对子宫胎盘的影响 功能“，涉及O·斯莱登博士、A·弗里亚斯博士和L·迈亚特博士。项目四，“雄激素过量导致脂肪生成” 与D.Dumesic博士和G.Chazenbalk博士在 加州大学洛杉矶分校妇产科。项目I-III将由非人灵长类(NHP)核心(O。 Slayden，Supervisor)作为封闭资源运行。这个核心将维持四个治疗组的女性 恒河猴(对照、睾丸素或T处理、WSD处理和T+WSD)再延长两年， 包括生育试验。则将支持测试去除T和WSD的效果的程序， 包括另一次生育试验。行政核心(R.Stouffer博士和J.Henneold博士)将指导 NCTRI的活动，并促进与其他中心和NICHD官员的互动。外展核心(D. 戈登和M·泽林斯基博士)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作用的重要新信息将单独和在 组合，与多囊卵巢综合征等生育障碍的病因学相关。此外，可逆性数据将提供 洞察新疗法的可能疗效，包括可能限制疗法的表观遗传学变化。 据估计，人类人口中的不孕不育率为9%，越来越多的证据表明 高雄激素血症或肥胖本身就会导致生殖功能障碍，两者结合在一起会进一步损害生育能力。 然而，雄激素的因果关系，特别是与生殖功能障碍有关的因素，是 有争议的。对灵长类动物和正常体重的多囊卵巢综合征女性的机制研究将区分这两个角色 了解慢性雄激素暴露和饮食，并为改善不孕不育的治疗提供洞察力。