Reproductive Endocrinology And Infertility Clinical Training Program

子宫肌瘤 在美国，超过50%的女性在生育年龄结束时会患上子宫肌瘤，这使这种疾病成为女性中最常见的生殖障碍。尽管这种情况很普遍，但人们对这种情况仍然知之甚少。子宫肌瘤的一个显著特征是肿瘤内的细胞产生无序和过度的细胞外基质(ECM)。以前，我们已经检查了细胞外基质和产生这种过度和纤维化的细胞外基质的细胞特征，并发现在肌瘤内的细胞中，机械信号(一种细胞沟通和激活的方法)发生了变化。我们发现，构成肌瘤的细胞对机械刺激的反应减弱(降低)。此外，我们完成了由MRI引导的高频超声(HIFU)的Wood、Stratton和Venkatesan博士领导的非手术治疗子宫肌瘤的合作临床试验。 不孕不育和生殖健康差距 我们单位继续进行不孕不育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距专题的特别利益小组和国家研究网络。该分会的研究人员帮助安排了今年美国生殖医学会年会上关于这种生殖健康差距的新的摘要会议和研讨会。在过去，我们的工作人员领导了由NICHD主办的关于健康差距的会议。同样是在过去的一年里，阿姆斯特朗博士和西格斯编辑了一期关于生殖健康差异的期刊。 BRX(又称AKAP13)在心脏发育、免疫功能和生殖中的作用 我们以前对本课题组克隆的BRX(AKAP13)基因的研究表明，这个大的Rho-egf原癌蛋白参与了雌激素和糖皮质激素受体的激活。我们先前发现，BRX基因产物在小鼠心肌细胞发育过程中协调G-亚α-S和Rho信号与一个必要的转录程序，涉及心肌细胞增强因子2C(MEF2C)。带有两个AKAP13基因缺陷拷贝(敲除)的小鼠在子宫中死亡。在过去的一年里，我们在利用Cre-Lox系统在小鼠身上开发条件基因靶向策略方面取得了进展。计划是检查有条件的目标后代的表型。此外，在接下来的一年里，我们将检查AKAP13零等位基因杂合子小鼠的表型，以确定这些小鼠是否在雌激素或糖皮质激素信号方面存在微妙的异常。

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. 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. 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 our staff has led an NICHD-hosted conference on Health Disparities. Also in the past year, Dr. Armstrong and Segars have edited a journal issue on Reproductive Health Disparities. 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.