OVARIAN FOLLICULOGENESIS

卵巢卵泡发生

• 批准号: 6108016
• 负责人: Lawrence M Nelson
• 金额: --
• 依托单位: EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6108016
• 关键词: autoantibody; autoimmune disorder; biopsy; bone density; clinical research; complementary DNA; developmental genetics; disease /disorder model; egg /ovum; female; fertility; gene expression; genetic library; genetically modified animals; graafian follicles; hormone regulation /control mechanism; human subject; laboratory mouse; luteinizing hormone; newborn animals; oogenesis; ovary disorder; ovulation; polycystic ovary syndrome

This project seeks to improve the clinical care available to patients with disorders of ovarian follicle function and ovulation through research using animal models as well as clinical protocols. In pursuing this goal, we expect to expand understanding of the ovarian follicle in health and disease. We have focused on premature ovarian failure, a condition that prematurely terminates ovarian function and fertility in 1% of women. We have particular interest in autoimmunity as a cause of ovarian failure. In a mouse model, we found that autoantibodies from mice with experimental autoimmune oophoritis bind to a 120 kd protein that is specific to the oocyte cytoplasm. Using this immune serum we identified a novel oocyte-specific gene that may represent the inciting antigen in this disease. In the clinic, we have found that premature ovarian failure is not merely a premature menopause. One half of these young women have ovaries that function intermittently. We successfully treated one woman with histologically proven autoimmune oophoritis under an approved research protocol using low dose prednisone. We have also demonstrated that inappropriate luteinization of graafian follicles is a major pathophysiologic mechanism preventing normal follicle function. We plan to develop therapeutic strategies to prevent this inappropriate luteinization and possibly restore fertility to some of these young women. In a related effort, we are investigating the physiology of the luteinization process in normal fertile women. We are also investigating other adverse health consequences of premature ovarian failure. We found that these young women have deficient circulating free testosterone levels, and, surprisingly, we found that two thirds of our patients have a reduced bone density that may place them at increased risk of hip fracture. Furthermore, we have preliminary findings to suggest that one-third of these young women may have an associated mineralocorticoid deficiency. Premature ovarian failure is clearly a more complex condition than has been previously recognized. We have clinical studies underway to develop hormone replacement methods appropriate specifically to these young women. We have also expanded our efforts to include clinical studies of polycystic ovary syndrome.

该项目旨在改善临床护理 可用于卵巢卵泡功能和 通过使用动物模型以及临床的研究排卵 协议。在追求这一目标时，我们希望扩大理解 健康和疾病中的卵巢卵泡。我们专注于 早产卵巢衰竭，过早终止的情况 1％的女性的卵巢功能和生育能力。我们有特殊之处 对自身免疫的兴趣是卵巢衰竭的原因。在鼠标中 模型，我们发现来自实验的小鼠的自身抗体 自身免疫性卵形炎与120 kD蛋白结合，该蛋白特有 卵母细胞细胞质。使用这种免疫血清，我们确定了 新型卵母细胞特异性基因，可能代表煽动抗原 这种疾病。在诊所中，我们发现卵巢早产 失败不仅是过早的更年期。其中的一半 年轻女性的卵巢间歇性发挥作用。我们 成功地对待一名经过组织学证明的女人 在经认可的研究方案下使用自身免疫性卵形病 低剂量泼尼松。我们还证明了不合适的 Graafian卵泡的黄体化是一种主要的病理生理学 防止正常卵泡功能的机制。我们计划发展 防止这种不适当的黄体和的治疗策略 可能会恢复其中一些年轻女性的生育能力。在 相关的工作，我们正在研究 正常育妇女的黄体化过程。我们也是 调查过早的其他不良健康后果 卵巢衰竭。我们发现这些年轻女性缺乏 循环免费睾丸激素水平，令人惊讶的是，我们发现 我们三分之二的患者的骨密度降低了 将它们置于增加髋部骨折的风险。此外，我们还有 初步的发现表明，这些年轻的三分之一 妇女可能患有相关的矿物皮质激素缺乏症。 早产卵巢衰竭显然比 以前已被认可。我们正在进行临床研究 为了开发适当的激素替代方法 对这些年轻女性。我们还扩大了我们的努力 包括多囊卵巢综合征的临床研究。