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: 7958881
• 负责人: MARTIN CADWALLADER
• 金额: $ 20.86万
• 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/7958881
• 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的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 描述（由申请人提供）：多囊卵巢综合征（PCOS）是最常见的女性内分泌疾病，可增加不孕症、2型糖尿病、心血管疾病和子宫内膜癌的终生风险。PCOS的病因仍然未知，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1年的试点研究，以解决这两个问题，利用我们的非人灵长类动物PCOS表型的鉴定和我们的潜在能力，以检测在人类婴儿中的PCOS的儿科前驱。目标1和目标2将采用生殖和身体测量评估来识别成年雌性食蟹猴和恒河猴中自发发生的雄激素过多、生育力/生殖力下降、多囊卵巢和抗苗勒管激素升高（多囊卵巢综合征的标志），从而允许对后者进行初步遗传性分析。目标3将在新生儿雄激素缺乏暴露的雌猴中发现的高雄激素表型转化为具有未来PCOS风险的人类婴儿女孩的鉴定，并将采用威斯康星州CTSA分析服务公司最近开发的质谱技术来确定胎儿暴露于人类婴儿头发中的雄激素过量，从而首次证实我们提出的PCOS发育起源。在目标4中组织的会议将评估研究结果并制定后续策略，以确定灵长类动物自发性PCOS的基础以及女性成年PCOS之前青春期前内分泌和代谢发育的改变轨迹。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PCOS。本次修订奖提交中提出的所有四个目标将加强威斯康星州国家灵长类动物研究中心（WNPRC）再生医学与生殖和衰老与代谢领域研究小组的PCOS研究的5年计划，而目标1-3将扩大P51父母补助金中WNPRC检测服务的具体目标3和4，以促进类固醇激素测定。 公共卫生相关性（由申请人提供）：在非人灵长类动物中鉴定多囊卵巢综合征（PCOS）将为确定这种导致不孕症、2型糖尿病和肥胖的普遍女性健康疾病的起源提供模型。测定头发中的睾酮将允许将这种非侵入性技术转化为临床识别有PCOS风险的新生女性婴儿。