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.


METHODS
Case-control study.


METHODS
University medical center.


METHODS
Thirty reproductive-aged women with submucosal, intramural, or no uterine myomas who underwent hysteroscopy or hysterectomy.


METHODS
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.


METHODS
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.


RESULTS
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.


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.
Rackow
Beth W
BW
Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06520-8063, USA. beth.rackow@yale.edu
Taylor
Hugh S
HS
D000328:Adult; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D010064:Embryo Implantation / Q000502:physiology; D004717:Endometrium / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D000080905:Homeobox A10 Proteins; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007247:Infertility, Female / Q000175:diagnosis / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism; D007889:Leiomyoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D053605:Leukemia Inhibitory Factor / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D009092:Mucous Membrane / Q000378:metabolism / Q000473:pathology*; D011379:Prognosis; D014594:Uterine Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*
D014408:Biomarkers, Tumor; C484298:HOXA11 protein, human; D000080905:Homeobox A10 Proteins; D018398:Homeodomain Proteins; C489676:KLF9 protein, human; D051741:Kruppel-Like Transcription Factors; C507837:LIF protein, human; D053605:Leukemia Inhibitory Factor; C069634:HOXA10 protein, human