The Unit on Reproductive Endocrinology and Infertility, led by James Segars, investigates underlying causes and effectiveness of treatment for a variety of clinical reproductive disorders. Our efforts have been focused on uterine leiomyoma (commonly known as fibroids), endometriosis, and reproductive disorders leading to infertility. The unit has the mission to conduct basic, translational, and clinical studies of importance to reproduction in the context of the multi-institutional clinical training program in Reproductive Endocrinology and Infertility. In the past year, we expanded upon our observation that the extracellular matrix of uterine fibroids was abnormally-formed. Based on several studies, our research suggests striking similarities common to fibroid development, keloid formation and altered tissue repair. This has led to the hypothesis that the altered extracellular matrix of uterine fibroids may contribute to fibroid growth. We plan to examine whether compounds that interfere with formation of excessive extracellular matrix similar to that observed in fibroids may have clinical utility. Also in the past year we have concluded a large prospective, randomized, placebo-controlled trial of the selective estrogen receptor modular(SERM), raloxifene, for the treatment of endometriosis-related chronic pelvic pain. This study headed by Dr. Stratton revealed that treatment with raloxifene actually hastened the return to pain in women with endometriosis, indicating that raloxifene, contrary to predictions, was not beneficial in this patient group. Our basic science studies in collaboration with Drs. Chrousos and Kino have revealed that the proto-oncoprotein cloned in our laboratory, Brx, is required for glucocorticoid action in vivo in some instances. This important observation indicates that Brx has a role beyond estrogen action, as initially understood, and may influence the action of other nuclear receptors, suggesting a possible importance for Brx for hormone action in tissues outside the reproductive tract.

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U.S. National Inst/Child Hlth/Human Dev
United States
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Chason, Rebecca J; Kang, Jung-Hoon; Gerkowicz, Sabrina A et al. (2015) GnRH agonist reduces estrogen receptor dimerization in GT1-7 cells: evidence for cross-talk between membrane-initiated estrogen and GnRH signaling. Mol Cell Endocrinol 404:67-74
Thorne, Jeffrey T; Segal, Thalia R; Chang, Sydney et al. (2015) Dynamic reciprocity between cells and their microenvironment in reproduction. Biol Reprod 92:25
Jorge, Soledad; Chang, Sydney; Barzilai, Joshua J et al. (2014) Mechanical signaling in reproductive tissues: mechanisms and importance. Reprod Sci 21:1093-107
Segars, James H (2014) Uterine fibroid research: a work in progress. Reprod Sci 21:1065-6
Connell, Mt; Owen, Cm; Segars, Jh (2013) Genetic Syndromes and Genes Involved in the Development of the Female Reproductive Tract: A Possible Role for Gene Therapy. J Genet Syndr Gene Ther 4:
Norian, John M; Owen, Carter M; Taboas, Juan et al. (2012) Characterization of tissue biomechanics and mechanical signaling in uterine leiomyoma. Matrix Biol 31:57-65
Beall, Stephanie A; DeCherney, Alan (2012) History and challenges surrounding ovarian stimulation in the treatment of infertility. Fertil Steril 97:795-801
Browne, Hyacinth N; Moon, Kimberly S; Mumford, Sunni L et al. (2011) Is anti-Müllerian hormone a marker of acute cyclophosphamide-induced ovarian follicular destruction in mice pretreated with cetrorelix? Fertil Steril 96:180-186.e2
Batcheller, April; Cardozo, Eden; Maguire, Marcy et al. (2011) Are there subtle genome-wide epigenetic alterations in normal offspring conceived by assisted reproductive technologies? Fertil Steril 96:1306-11
Mayers, Chantal M; Wadell, Jennifer; McLean, Kate et al. (2010) The Rho guanine nucleotide exchange factor AKAP13 (BRX) is essential for cardiac development in mice. J Biol Chem 285:12344-54

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