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.
Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06520-8063, USA. beth.rackow@yale.edu
Beth W
BW
Rackow
Hugh S
HS
Taylor
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