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

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 center. PATIENT(S): Thirty reproductive-aged women with submucosal, intramural, or no uterine myomas who underwent hysteroscopy or hysterectomy. INTERVENTION(S): 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 MEASURE(S): Endometrial HOXA10 expression was evaluated as a primary endpoint using quantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry. HOXA11, BTEB1, and LIF were evaluated using real-time RT-PCR. RESULT(S): Endometrial HOXA10 and HOXA11 messenger RNA (mRNA) expression were significantly decreased in uteri with submucosal myomas compared with controls and with 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. CONCLUSION(S): 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.