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

Fertil Steril. 2010 Apr;93(6):2027-34. doi: 10.1016/j.fertnstert.2008.03.029. Epub 2008 Jun 13.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Biomarkers, Tumor / genetics*
  • Biomarkers, Tumor / metabolism
  • Case-Control Studies
  • Embryo Implantation / physiology
  • Endometrium / metabolism
  • Endometrium / pathology
  • Endometrium / physiopathology*
  • Female
  • Gene Expression Regulation, Neoplastic / physiology
  • Homeobox A10 Proteins
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • Humans
  • Infertility, Female / diagnosis
  • Infertility, Female / etiology*
  • Infertility, Female / genetics
  • Infertility, Female / metabolism
  • Kruppel-Like Transcription Factors / genetics
  • Kruppel-Like Transcription Factors / metabolism
  • Leiomyoma / genetics
  • Leiomyoma / metabolism
  • Leiomyoma / pathology
  • Leiomyoma / physiopathology*
  • Leukemia Inhibitory Factor / genetics
  • Leukemia Inhibitory Factor / metabolism
  • Middle Aged
  • Mucous Membrane / metabolism
  • Mucous Membrane / pathology*
  • Prognosis
  • Uterine Neoplasms / genetics
  • Uterine Neoplasms / metabolism
  • Uterine Neoplasms / pathology
  • Uterine Neoplasms / physiopathology*


  • Biomarkers, Tumor
  • HOXA11 protein, human
  • Homeobox A10 Proteins
  • Homeodomain Proteins
  • KLF9 protein, human
  • Kruppel-Like Transcription Factors
  • LIF protein, human
  • Leukemia Inhibitory Factor
  • HOXA10 protein, human