Reproductive Endocrinology And Infertility Clinical Training Program

子宫肌瘤 到生育年龄结束时，美国超过50%的女性患上子宫肌瘤，使其成为女性最普遍的生殖障碍。尽管这种疾病普遍存在，但人们对这种疾病的了解仍然很少。子宫肌瘤的一个突出特征是肿瘤内的细胞产生紊乱和过量的细胞外基质（ECM）。以前，我们已经检查了ECM和产生这种过度和纤维化ECM的细胞的特征，并发现机械信号（细胞通讯和激活的方法）在肌瘤内的细胞中发生了改变。在过去的一年中，我们发现，构成纤维瘤的细胞对机械刺激的反应受损（降低）。此外，我们完成了一项由Wood、Stratton和Venkatesan博士领导的关于MRI引导的高频超声（HIFU）用于子宫肌瘤非手术治疗的合作临床试验。 接受癌症治疗的妇女和年轻女孩的卵巢功能评估和保护 由于提高了生存率和有效的癌症化疗，许多年轻女孩和妇女现在能够从癌症中幸存下来，但发现生殖功能受损。在过去的一年中，我们已经完成了动物和临床研究，计划继续在儿科临床人群中进行额外的研究，并进行额外的动物研究，以检查暴露于烷化剂后原始卵泡保存的潜在机制。我们还将继续研究不孕症患者卵巢储备功能下降的情况。在过去的一年里，我们报告了动物数据，表明GnRH类似物在暴露于化疗药物环磷酰胺后保留了原始卵泡。 结果表明，这可能是由于细胞凋亡（程序性细胞死亡）减少。在未来一年，我们计划继续调查可能涉及的机制。我们还计划开始一项临床研究，在这一患者人群中检测卵巢储备的新生物标志物。 不孕症和生殖健康差距 我们的单位继续进行不孕症和生殖健康差距的研究。阿姆斯特朗博士帮助建立了一个关于健康差异问题的特别兴趣小组和国家研究网络。 分支的研究人员帮助安排了一个新的摘要会议和研讨会，今年在美国生殖医学学会年会上讨论这种生殖健康的差异。 在过去的一年里，阿姆斯特朗博士还领导了一个由NICHD主办的关于健康差距的会议。在接下来的一年里，我们计划继续研究血脂和葡萄糖代谢的种族和种族差异。 BRX（也称为AKAP 13）在心脏发育，免疫功能和生殖中的作用 我们以前的研究基因BRX（AKAP 13），由我们的小组克隆，表明这个大的Rho-GEF原癌蛋白参与雌激素和糖皮质激素受体的激活。我们以前发现，BRX基因产物协调G-亚-α-s和Rho信号转导与小鼠心肌细胞发育中的一个重要转录程序，涉及肌细胞增强因子2C（MEF 2C）。AKAP 13基因（敲除）有两个缺陷拷贝的小鼠在子宫内死亡。在过去的一年中，我们已经取得了进展，在小鼠中使用Cre-Lox系统的条件基因靶向策略的发展。计划是检查有条件靶向后代的表型。此外，在接下来的一年里，我们将检查AKAP 13无效等位基因杂合小鼠的表型，以确定这些小鼠是否可能在雌激素或糖皮质激素信号传导方面存在细微异常。

Uterine leiomyoma By the end of their reproductive years, over 50% of women in the United States develop uterine fibroids, making the condition the most prevalent reproductive disorder of women. Despite their prevalence, the condition remains poorly understood. One prominent feature of uterine fibroids is that cells within the tumors produce a disordered and excessive extracellular matrix (ECM). Previously, we have examined the ECM and characteristics of the cells that produce this excessive and fibrotic ECM and have found that mechanical signaling (a method of cell communication and activation) was altered in cells within a fibroid. In the past year we have found that cells that comprise a fibroid have impaired responses (decreased) to mechanical stimuli. Additionally, we completed a collaborative clinical trial led by Drs. Wood, Stratton and Venkatesan of MRI-guided high frequency ultrasound (HIFU) for the non-surgical treatment of uterine fibroids. Assessment and preservation of ovarian function in women and young girls undergoing cancer treatment Because of improved survival and effective chemotherapy for cancers, many young girls and women now are able to survive cancer, but find that reproductive function is impaired. In the past year we have completed animal and clinical investigations with plans to continue additional studies in a pediatric clinical populations and additional animal studies to examine potential mechanism(s) for preservation of primordial follicles after exposure to alkylating agents. We will also continue our study of diminished ovarian reserve in infertility patients. In the past year we reported animal data that suggested GnRH analogues preserve primordial follicles after exposure to the chemotherapy agent, cyclophosphamide. Results suggested that this may be due to a decrease in apoptosis (programmed cell death). In the coming year, we plan to continue to investigate possible mechanism(s) involved. We also plan to begin a clinical study to examine new biomarkers of ovarian reserve in this patient population. Infertility and reproductive health disparities Our unit has continued to conduct studies of infertility and reproductive health disparities. Dr. Armstrong helped to established a Special Interest Group and national research network on the topic of Health Disparities. Investigators in the branch helped to arrange the a new abstract session and symposium this year at the Annual Meeting of the American Society of Reproductive Medicine on this reproductive health disparities. In the past year, Dr. Armstrong also led an NICHD-hosted conference on Health Disparities. In the coming year, we plan to continue to examine ethnic and racial differences in lipids and glucose metabolism. Role of BRX (also known as AKAP13) in cardiac development, immune function and reproduction Our previous studies of the gene BRX (AKAP13), cloned by our group, indicated that this large Rho-GEF protooncoprotein was involved in estrogen and glucocorticoid receptor activation. We previously found that the BRX gene product coordinates G-sub-alpha-s and Rho signaling with an essential transcription program in developing cardiomyocytes in mice, involving myocyte enhancer factor 2 C (MEF2C). Mice with two defective copies of the AKAP13 gene (knockout) died in utero. In the past year we have made progress on development of a conditional gene targeting strategy using the Cre-Lox system in mice. Plans are to examine the phenotypes of the conditionally-targeted offspring. In addition, in the coming year we will examine the phenotypes of mice heterozygous for the AKAP13 null allele to determine whether these mice may have subtle abnormalities in estrogen or glucocorticoid signaling.