Uterine leiomyoma, commonly called fibroids, are one of the most common and prevalent diseases of the female reproductive tract.Some leiomyoma are associated with rare genetic syndromes, such as Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC). In order to learn whether the cellular events associated with HLRCC-associated leiomyoma resembled common or nonsyndromic leiomyoma, in the past year we used gene profiling experiments to compare the two types of leiomyoma. We found that while both types of leiomyoma had low levels of fumarate hydratase, there was a significant overexpression of glycolysis enzymes in the HLRCC-syndromic leiomyoma compared to common leiomyoma. We confirmed overexpression of these genes with real-time reverse-transcriptase PCR. Interestingly, overexpression of the glycolysis enzymes was consistent throughout the glycolysis pathway, with the exception of phosphoglycerate kinase in one HLRCC specimen. We interpret the findings to suggest that the glycolysis pathway is up-regulated in HLRCC leiomyoma, whereas the Krebs cycle function was diminished due to the low levels of fumarate hydratase. In short, these results indicate that while leiomyoma associated with rare syndromes may physically resemble common nonsyndromic leiomyoma, there are marked differences between the tumors.? ? Diagnosis of endometriosis represents a problem for patients and providers since surgery is required, but one persistent question is the appearance of endometriosis lesions at surgery. In the past year Drs. Stratton and Stegmann correlated biopsy result with lesion appearance in order to determine the characteristics of lesions most likely to represent endometriosis. The results showed that, in contrast to prevailing opinion, no single colot had a high association with endometriosis and that surgeons operating on women with endometriosis should consider and biopsy any suspicious lesion. Specifically, subtle lesions were nearly as likely to contain endometriosis as were those that were black or of mixed colors. Overall, the lesions most likely to contain pathologically-confirmed disease were those that were >10mm in width and >5mm in depth. However, experienced surgeons were only able to correctly identify lesions 64% of the time. This study suggests that biopsy, not visual inspection, should remain the gold standard for disease diagnosis. ? ? Reproductive health disparities exist for many women. Our unit has been interested in examining the causes and consequences of these disparities in an effort to devise strategies to optimize reproductive outcome across racial and ethnic groups. One health disparity idenfied was outcome of infertility treatments. Recently we found that the different incidence of leiomyoma in African-American women explained, at least in part, reduction in pregnancy outcome with assisted reproduction. In the past year we evaluated ART utilization and outcome among Hispanic couples. This study suggested that contrary to claims of some that economic barriers accounted for lower rates of utilization, other factors were responsible. In the coming year we plan to initiate a multicenter trial to assess disparities and utilization of infertility services.

Project Start
Project End
Budget Start
Budget End
Support Year
7
Fiscal Year
2007
Total Cost
$643,120
Indirect Cost
City
State
Country
United States
Zip Code
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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