Submucosal uterine leiomyomas have a global effect on molecular determinants of endometrial receptivity

Abstract

Study objective-To evaluate the effect of uterine leiomyomas on the endometrium using molecular markers of endometrial receptivity: HOXA10, HOXA11, LIF, and BTEB1. Design-Case-control study Setting-University medical centerPatients-Thirty reproductive-age women with submucosal, intramural, or no uterine myomas who underwent hysteroscopy or hysterectomy.Interventions-Proliferative phase endometrial sampling was performed at the time of surgery. In uteri with a submucosal myoma, directed endometrial biopsies were obtained over the myoma and over normal myometrium.Main outcome measures-Endometrial HOXA10 expression was evaluated as a primary end point using quantitative real time RT-PCR and immunohistochemistry. HOXA11, BTEB1, and LIF were evaluated using real time RT-PCR.Results-Endometrial HOXA10 and HOXA11 mRNA expression were significantly decreased in uteri with submucosal myomas compared to controls and to uteri with intramural myomas. A similar trend was seen in BTEB1 mRNA expression, however no difference was found in LIF mRNA expression. Immunohistochemistry localized the decrease in endometrial HOXA10 protein expression to stroma. In the presence of a submucosal myoma, there were no regional differences in gene expression.Conclusions-The molecular mechanism by which submucosal myomas adversely affect reproduction includes a global decrease in endometrial HOX gene expression, not simply a focal change over the myoma. This may explain the reproductive dysfunction observed with submucosal myomas.

The Role ofHoxGenes in Female Reproductive Tract Development, Adult Function, and Fertility

“…HOXA10 is expressed in human myometrium and its expression also has a menstrual cycledependent pattern. In vitro, HOXA10 expression is induced in endometrial stromal cells by progesterone, but in the primary myometrial cells, progesterone suppresses HOXA10 expression (Cermik et al 2001;Matsuzaki et al 2009;Rackow and Taylor 2010;Sinclair et al 2011). It is clear that there are different factors involved in the regulation of HOXA10 by progesterone in myometrium than endometrium.…”

The Usefullness of Office Hysteroscopy in Evaluation of Infertil Women Prior to In Vitro Fertilization Cycles

“…Miyomların subfertilite ile ilişkili oldukları, endometriyal kaviteyi düzensizleştirdikleri, tubal ostiumların pasajını engelleyebildikleri, kaviteyi torsiyone ederek implantasyonu bozdukları, ayrıca uterin kontraktiliteyi artırdıkları, lokal inflamasyona neden oldukları ve vasküler yapılarda deği-şikliklere neden olarak endometriyal reseptiviteyi azalttıkları iddia edilmiştir. 15 Cerrahi olarak yapı-lan miyomektominin fertiliteyi ve gebelik oranlarını artırdığı ve abortusları da azalttığı yapılan bir meta-analizde gösterilmiştir. 16 Endometriyal poliplerin çoğu asemptomatik olduğu için populasyondaki sıklığının tespiti yapı-lamamıştır.…”

Modern approaches to endometrial receptivity assessment (a review)

“…По данным ряда авторов [67], экспрессия НОХА-10 гена, участвующего в регу-ляции роста, дифференциации и рецептивности эн-дометрия, оказывается сниженной в период «окна имплантации» у пациенток с подтвержденной без-успешностью имплантации. Предполагается, что снижение экспрессии НОХА-10 (спровоцированное, например, его гиперметилированием) может приво-дить к устойчивости действия прогестерона в эндоме-трии, так как в норме НОХ-гены модулируют многие функции прогестерона [68].…”