Cited by 284Endometriosis Research and TreatmentEpigenetics and DNA MethylationReproductive System and Pregnancy

Aberrant methylation at HOXA10 may be responsible for its aberrant expression in the endometrium of patients with endometriosis

Wu, Yan, Halverson, Gloria, Basir, Zainab, Strawn, Estil, Yan, Pearlly, Guo, Sun-Wei·2005·American Journal of Obstetrics and Gynecology

Abstract

Objective HOXA10, expressed in endometrium, plays an important role in uterine receptivity at the time of implantation. In the endometrium of women with endometriosis, its expression is reduced. The aim of this study was to determine whether the observed aberrant expression of HOXA10 is caused by aberrant methylation of the gene.Study design Endometrial tissues were collected from 6 women with laparoscopically confirmed endometriosis, and 4 women who underwent tubal ligation and were confirmed to have no endometriosis. In addition, menstrual blood from 5 women with no gynecologic complaints was collected and also used as controls. Methylation-specific polymerase chain reaction (PCR) and bisulfite sequencing were performed in 3 fragments in 2 regions of HOXA10 to detect difference in methylation patterns. Real-time reverse transcriptase (RT)-PCR was also performed to measure expression levels of HOXA10 in select cases and controls.Results In all 3 fragments, there were highly statistically significant differences in methylation patterns between women with endometriosis and those without endometriosis. The expression level of HOXA10 was lower in women with endometriosis than those without, as previously reported.Conclusion There is aberrant methylation in the endometrium of women with endometriosis compared with those without endometriosis. The aberrant methylation at HOXA10 may be responsible for the aberrant gene expression in the endometrium of women with endometriosis. This finding suggests that endometriosis may also be an epigenetic disease.

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Crossref · 10.1016/j.ajog.2005.01.034

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  • These endometrial cells exhibit hypermethylation of the PR-B promoter, inducing expression of the receptor protein and resulting in progesterone resistance.

    “these endometrial cells also exhibit hypermethylation of the PR-B promoter, inducing expression of the receptor protein [38,39,40] and finally resulting in a state of progesterone resistance.”
  • In eutopic endometrial cells of endometriosis patients, HOXA-10 does not show increased expression after ovulation due to hypermethylation and gene silencing of its promoter.

    “In eutopic endometrial cells of endometriosis patients, HOXA-10 does not show increased expression after ovulation due to hypermethylation and gene silencing of its promoter [39].”
  • Epigenetic modification is a possible mechanism by which the expression of genes necessary for the establishment of endometriosis is altered.

    “Epigenetic modification is a possible mechanism by which the expression of genes necessary for the establishment of endometriosis is altered.11,12”

    From Altered genome-wide methylation in endometriosis (2014) · cites this paper as [12]

  • Hypermethylation of MGMT has been reported to decrease apoptotic responses to DNA damage by TP73 and cell proliferation regulation by RBBP7, which in combination with aberrant expression of HOXA10, increase susceptibility for endometriosis.

    “The hypermethylation of methyltransferase (MGMT) has been reported to decrease apoptotic responses to DNA damage by TP73 and cell proliferation regulation by RBBP7, which in combination with the aberrant expression of HOXA10, increase the susceptibility for endometriosis.12,[41][42][43][44][45][46][47][48]”

    From Altered genome-wide methylation in endometriosis (2014) · cites this paper as [12]

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Authors
Wu, Y., Halverson, G., Basir, Z., Strawn, E., Yan, P., & Guo, S.-W.
Affiliations
  • Medical College of Wisconsin (US)
  • The Ohio State University (US)
Corresponding author
Guo, Sun-Wei
Venue
American Journal of Obstetrics and Gynecology
Publisher
Elsevier BV
Published
2005-08
Volume
193
Issue
2
Pages
371-380
ISSN
0002-9378 (ISSN-L)
OpenAlex
W2076128837
Cited by
283
References
42
Citations by year
2026: 3 · 2025: 11 · 2024: 10 · 2023: 22 · 2022: 13 · 2021: 8 · 2020: 14 · 2019: 18 · 2018: 13 · 2017: 10 · 2016: 23 · 2015: 15 · 2014: 18 · 2013: 16 · 2012: 15
FWCI
8.36
Type
journal article
Language
en
Open access
closed
Locations
  • American Journal of Obstetrics and Gynecology (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Reproductive Medicine › Endometriosis Research and Treatment
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
  • Life Sciences › Immunology and Microbiology › Immunology › Reproductive System and Pregnancy
Keywords
endometriosis, HOXA10, DNA methylation, aberrant gene expression, endometrium, epigenetics, endometrial receptivity, implantation, methylation-specific PCR, bisulfite sequencing
MeSH terms
Homeobox A10 Proteins, Base Sequence, DNA-Binding Proteins, Endometriosis, Endometrium, Female, Humans, Polymerase Chain Reaction, Homeodomain Proteins, DNA Methylation, Reverse Transcriptase Polymerase Chain Reaction, Epigenesis, Genetic

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