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.

Project Start
Project End
Budget Start
Budget End
Support Year
13
Fiscal Year
2013
Total Cost
$1,048,450
Indirect Cost
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State
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Tal, Reshef; Segars, James H (2014) The role of angiogenic factors in fibroid pathogenesis: potential implications for future therapy. Hum Reprod Update 20:194-216
Greene, Alexis D; Patounakis, George; Segars, James H (2014) Genetic associations with diminished ovarian reserve: a systematic review of the literature. J Assist Reprod Genet 31:935-46
Jorge, Soledad; Chang, Sydney; Barzilai, Joshua J et al. (2014) Mechanical signaling in reproductive tissues: mechanisms and importance. Reprod Sci 21:1093-107
Malik, Minnie; Britten, Joy; Segars, James et al. (2014) Leiomyoma cells in 3-dimensional cultures demonstrate an attenuated response to fasudil, a rho-kinase inhibitor, when compared to 2-dimensional cultures. Reprod Sci 21:1126-38
Leppert, Phyllis C; Jayes, Friederike L; Segars, James H (2014) The extracellular matrix contributes to mechanotransduction in uterine fibroids. Obstet Gynecol Int 2014:783289
Clark, Natalie A; Mumford, Sunni L; Segars, James H (2014) Reproductive impact of MRI-guided focused ultrasound surgery for fibroids: a systematic review of the evidence. Curr Opin Obstet Gynecol 26:151-61
Yu, Bo; Mumford, Sunni; Royster 4th, G Donald et al. (2014) Cost-effectiveness analysis comparing continuation of assisted reproductive technology with conversion to intrauterine insemination in patients with low follicle numbers. Fertil Steril 102:435-9
Segars, James H; Parrott, Estella C; Nagel, Joan D et al. (2014) Proceedings from the Third National Institutes of Health International Congress on Advances in Uterine Leiomyoma Research: comprehensive review, conference summary and future recommendations. Hum Reprod Update 20:309-33
Aagaard, Kjersti M; Segars, James H (2014) What is the microbiome and how do we study it? Semin Reprod Med 32:3-4
Sauerbrun-Cutler, May-Tal; Segars, James H (2013) Do in utero events contribute to current health disparities in reproductive medicine? Semin Reprod Med 31:325-32

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