Reproductive Endocrinology And Infertility Clinical Training Program

生殖内分泌与不孕不育临床培训项目

• 批准号: 8736973
• 负责人: James H. Segars
• 金额: $ 104.85万
• 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/8736973
• 关键词: AKAP13 gene; Alleles; American; Cardiac; Cardiac Myocytes; Cell Communication; Cells; Characteristics; Clinical; Clinical Research; Clinical Trials; Development; Disease; Estrogen Receptors; Estrogens; Extracellular Matrix; Fellowship Program; Fibroid Tumor; Frequencies; Gene Targeting; Genetic Transcription; Glucocorticoid Receptor; Glucocorticoids; Infertility; Infertility study; Journals; Knock-out; Magnetic Resonance Imaging; Mechanics; Methods; Mus; National Institute of Child Health and Human Development; Phenotype; Prevalence; Proteins; Receptor Activation; Reproduction; Reproductive Endocrinology; Reproductive Health; Reproductive Medicine; Research; Research Personnel; Role; Signal Transduction; Societies; Stimulus; System; Training Programs; Ultrasonography; United States; Uterine Fibroids; Woman; Wood material; abstracting; clinically relevant; endometriosis; health disparity; immune function; in utero; meetings; myocyte-specific enhancer-binding factor 2; offspring; programs; reproductive; response; rho; special interest group; symposium; tumor

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.

子宫肌瘤 到生育年龄结束时，超过 50% 的美国女性会患上子宫肌瘤，使这种疾病成为女性最常见的生殖疾病。尽管这种情况很普遍，但人们对这种情况仍然知之甚少。子宫肌瘤的一个显着特征是肿瘤内的细胞产生紊乱且过多的细胞外基质（ECM）。之前，我们检查了 ECM 以及产生这种过度纤维化 ECM 的细胞的特征，并发现肌瘤内细胞的机械信号（一种细胞通讯和激活的方法）发生了改变。我们发现构成肌瘤的细胞对机械刺激的反应受损（下降）。此外，我们完成了由博士领导的合作临床试验。 Wood、Stratton 和 Venkatesan 提出了 MRI 引导的高频超声 (HIFU) 用于子宫肌瘤的非手术治疗。 不孕不育和生殖健康差异 我们单位继续对不孕不育和生殖健康差异进行研究。阿姆斯特朗博士帮助建立了一个关于健康差异主题的特别兴趣小组和国家研究网络。 该分会的研究人员今年在美国生殖医学会年会上帮助安排了一次新的摘要会议和研讨会，讨论生殖健康差异。 过去，我们的工作人员曾主持过 NICHD 主办的健康差异会议。同样在去年，阿姆斯特朗博士和西格斯编辑了一份关于生殖健康差异的期刊。 BRX（也称为 AKAP13）在心脏发育、免疫功能和生殖中的作用 我们之前对我们小组克隆的基因 BRX (AKAP13) 的研究表明，这种大的 Rho-GEF 原癌蛋白参与雌激素和糖皮质激素受体的激活。我们之前发现，BRX 基因产物通过小鼠心肌细胞发育过程中的重要转录程序协调 G-sub-alpha-s 和 Rho 信号传导，其中涉及肌细胞增强因子 2 C (MEF2C)。带有两个 AKAP13 基因缺陷拷贝（敲除）的小鼠在子宫内死亡。去年，我们在小鼠体内使用 Cre-Lox 系统开发条件基因靶向策略方面取得了进展。计划检查有条件靶向的后代的表型。此外，明年我们将检查 AKAP13 无效等位基因杂合小鼠的表型，以确定这些小鼠的雌激素或糖皮质激素信号传导是否可能存在细微异常。