Format

Send to:

Choose Destination
See comment in PubMed Commons below
Semin Reprod Med. 2010 Jan;28(1):69-74. doi: 10.1055/s-0029-1242996. Epub 2010 Jan 26.

Molecular mechanisms of treatment resistance in endometriosis: the role of progesterone-hox gene interactions.

Author information

  • 1Department of Obstetrics, Gynecology & Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut 06520-8063, USA.

Abstract

HOX genes, encoding homeodomain transcription factors, are dynamically expressed in endometrium, where they are necessary for endometrial growth, differentiation, and implantation. In human endometrium, the expression of HOXA10 and HOXA11 is driven by sex steroids, with peak expression occurring at time of implantation in response to rising progesterone levels. However, the maximal HOXA10 and HOXA11 expression fails to occur in women with endometriosis. In endometriosis, altered progesterone receptor expression or diminished activity may lead to attenuated or dysregulated progesterone response and decreased expression of progesterone-responsive genes including HOX genes in the eutopic endometrium. In turn, other mediators of endometrial receptivity that are regulated by HOX genes, such as pinopodes, alphavbeta3 integrin, and IGFBP-1, are downregulated in endometriosis. HOXA10 hypermethylation has recently been demonstrated to silence HOXA10 gene expression and account for decreased HOXA10 in the endometrium of women with endometriosis. Silencing of progesterone target genes by methylation is an epigenetic mechanism that mediates progesterone resistance. The relatively permanent nature of methylation may explain the widespread failure of treatments for endometriosis-related infertility.

PMID:
20104430
[PubMed - indexed for MEDLINE]
PMCID:
PMC3107856
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Georg Thieme Verlag Stuttgart, New York Icon for PubMed Central
    Loading ...
    Write to the Help Desk