DETERMINING PCOS-LIKE TRAITS IN MACAQUES AND NEWBORN HUMAN INFANTS

确定猕猴和新生儿的 PCOS 样特征

• 批准号: 7958880
• 负责人: MARTIN CADWALLADER
• 金额: $ 29.59万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-25 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7958880
• 关键词: Address; Adult; Aging; Androgens; Animal Model; Area; Award; Biological Assay; Cardiovascular Diseases; Childhood; Clinical; Computer Retrieval of Information on Scientific Projects Database; Development; Disease; Endocrine; Endometrial Carcinoma; Etiology; Exposure to; Female; Fertility; Funding; Future; Grant; Hair; Head; Heritability; Human; Human Identifications; Infant; Infertility; Institution; Macaca; Macaca mulatta; Mass Spectrum Analysis; Metabolic; Metabolism; Modeling; Monkeys; Newborn Infant; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Outcome Study; Perinatal Exposure; Phenotype; Pilot Projects; Polycystic Ovary Syndrome; Primates; Regenerative Medicine; Reproduction; Research; Research Personnel; Resources; Risk; Services; Source; Techniques; Testosterone; Translating; Translations; United States National Institutes of Health; Wisconsin; Woman; Women' s Health; base; follow-up; human female; lifestyle intervention; lifetime risk; meetings; mullerian-inhibiting hormone; nonhuman primate; novel therapeutics; parent grant; prevent; public health relevance; reproductive; steroid hormone; trait

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. DESCRIPTION (provided by applicant): Polycystic ovary syndrome (PCOS) is the most prevalent women's endocrinopathy conferring increased lifetime risk of infertility, type 2 diabetes, cardiovascular disease and endometrial cancer. The etiology of PCOS remains unknown due, in part, to the lack of (1) a naturally-occurring animal model and (2) a pediatric phenotype. We propose to initiate a 1-year pilot study to address both issues by capitalizing on our identification of nonhuman primate PCOS phenotypes and our potential ability to detect a pediatric antecedent to PCOS in human infants. Aims 1 and 2 will employ reproductive and somatometric assessments to identify spontaneously occurring androgen excess, diminished fertility/fecundity, polycystic ovaries and elevated anti-mullerian hormone (hallmarks of PCOS) in adult female cynomolgus and rhesus macaques permitting initial heritability analyses in the latter. Aim 3 will translate the hyperandrogenic phenotype found in newborn infant androgeri-exposed female monkeys into identification of human infant giris with risk of future PCOS, and will engage mass spectrometry techniques recently developed by the Wisconsin CTSA Assay Services to determine fetal exposure to androgen excess in a lock of human infant head hair, thus providing the first confirmation of our proposed developmental origins for PCOS. The meeting organized in Aim 4 will evaluate study outcomes and devise follow-up strategies to identify the basis for spontaneous PCOS in primates and altered trajectory of pre-pubertal endocrine and metabolic development that precedes adult PCOS in women. The overall aim is to translate Primate Center and CTSA expertise and resources into novel therapeutic or lifestyle interventions to prevent PCOS in adulthood. All four Aims proposed in this Revision Award submission will strengthen the 5-year plans for PCOS research in both the Regenerative Medicine & Reproduction and Aging & Metabolism Area research groups at the Wisconsin National Primate Research Center (WNPRC), while Aims 1-3 will expand Specific Aims 3 and 4 of WNPRC Assay Services in the P51 parent grant with regard to advances in steroid hormone determination. PUBLIC HEALTH RELEVANCE (provided by applicant): Identification of polycystic ovary syndrome (PCOS) in nonhuman primates will provide models for determining the origins ofthis prevalent women's health disorder resulting in infertility, type 2 diabetes and obesity. Determining testosterone in head hair will permit translation of this noninvasive technique into clinical identification of newborn human female infants at risk for PCOS.

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 描述(申请人提供)：多囊卵巢综合征(PCOS)是最常见的女性内分泌疾病，会增加终生不孕、2型糖尿病、心血管疾病和子宫内膜癌的风险。多囊卵巢综合征的病因仍不清楚，部分原因是缺乏(1)自然发生的动物模型和(2)儿科表型。我们建议启动一项为期一年的试点研究来解决这两个问题，方法是利用我们对非人类灵长类PCOS表型的鉴定，以及我们在人类婴儿中检测多囊卵巢综合征的儿科先驱的潜在能力。AIMS 1和AIMS 2将使用生殖和身体测量评估，以确定成年雌性食蟹猴和恒河猴中自然发生的雄激素过多、生育力/繁殖力下降、多囊卵巢和抗苗勒氏激素升高(PCOS的特征)，从而允许对后者进行初步遗传力分析。Aim 3将在暴露于雄激素的新生婴儿雌性猴子中发现的高雄激素表型转化为识别具有未来多囊卵巢综合征风险的人类女婴，并将采用威斯康星州CTSA化验服务最近开发的质谱仪技术来确定胎儿暴露于一束人类婴儿头发中过量的雄激素，从而首次证实了我们提出的多囊卵巢综合征的发育起源。在Aim 4组织的会议将评估研究结果并制定后续战略，以确定灵长类动物自发性多囊卵巢综合征的基础，以及女性青春期前内分泌和代谢发展的改变轨迹。总体目标是将灵长类中心和CTSA的专业知识和资源转化为新的治疗或生活方式干预措施，以预防成年后的多囊卵巢综合征。这份修订奖申请中提出的所有四个AIMS将加强威斯康星州国家灵长类研究中心(WNPRC)再生医学和生殖以及衰老和新陈代谢领域研究小组的PCOS研究的五年计划，而AIMS 1-3将在P51父母拨款中扩大WNPRC检测服务的特定AIMS 3和4，涉及类固醇激素测定的进展。 公共卫生相关性(由申请人提供)：在非人类灵长类动物中识别多囊卵巢综合征(PCOS)将为确定这种导致不孕不育、2型糖尿病和肥胖症的普遍女性健康疾病的起源提供模型。通过检测头发中的睾丸素，可以将这种非侵入性技术转化为临床识别有多囊卵巢综合征风险的新生儿。