Altered expression of HOXA10 in endometriosis: potential role in decidualization
Abstract
Endometriosis is a poorly understood gynaecologic disorder that is associated with infertility. In this study, we examined the expression of HOXA10 in the eutopic endometrium of baboons with induced endometriosis. A decrease in HOXA10 mRNA was observed after 3, 6, 12 and 16 months of disease, which reached statistical significance at 12 and 16 months. HOXA10 protein levels were decreased in both the epithelial and stromal cells of the endometrium. Furthermore, expression of beta3 integrin (ITGB3), which is upregulated by HOXA10, was decreased, whereas EMX2, a gene that is inhibited by HOXA10, was increased. Next, methylation patterns of the HOXA10 gene were analysed in the diseased and control animals. The F1 region on the promoter was found to be the most significantly methylated in the endometriosis animals and this may account for the decrease in HOXA10 expression. Finally, we demonstrate that stromal cells from the eutopic endometrium of baboons with endometriosis expressed significantly higher levels of insulin-like growth factor binding protein-1 (IGFBP1) mRNA than disease-free animals in response to estradiol, medroxyprogesterone acetate and dibutyryl cAMP (H + dbcAMP). The functional role of HOXA10 in IGFBP1 expression was further explored using human endometrial stromal cells (HSC). Overexpression of HOXA10 in HSC resulted in a decrease of IGFBP1 mRNA, whereas silencing HOXA10 caused an increase of IGFBP1 mRNA, even in the presence of H + dbcAMP. These data demonstrate that HOXA10 negatively influences IGFBP1 expression in decidualizing cells. Thus, the decrease in HOXA10 levels may in part be involved with the altered uterine environment associated with endometriosis.
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The endometrium of women with endometriosis responds differently to ovarian hormones.
“It is important to emphasize that the endometrium of women with endometriosis has been documented to respond differently to ovarian hormones (83-86), and we can use this fact to discover new potential biomarkers through minimally invasive means (87).”
From Biomarkers in endometriosis: Challenges and opportunities (2017) · cites this paper as [84]
HOXA10 expression is lower in the endometrium of women with endometriosis and is abnormally methylated.
“We have previously shown that HOXA10 expression is lower in the endometrium of women with endometriosis and is abnormally methylated.44,53,54”
From Altered genome-wide methylation in endometriosis (2014) · cites this paper as [54]
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- Authors
- Kim, J. J., Taylor, H. S., Lu, Z., Ladhani, O., Hastings, J. M., Jackson, K. S., Wu, Y., Guo, S. W., & Fazleabas, A. T.
- Affiliations
- Northwestern University (US)
- Yale University (US)
- University of Illinois Chicago (US)
- Medical College of Wisconsin (US)
- Corresponding author
- Kim, J.Julie
- Venue
- MHR: Basic science of reproductive medicine
- Publisher
- Oxford University Press (OUP)
- Published
- 2007-03-09
- Volume
- 13
- Issue
- 5
- Pages
- 323-332
- ISSN
- 1360-9947 (ISSN-L)
- 1460-2407
- OpenAlex
- W2137799669
- Cited by
- 228
- References
- 71
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 6 · 2023: 9 · 2022: 9 · 2021: 13 · 2020: 2 · 2019: 8 · 2018: 15 · 2017: 11 · 2016: 19 · 2015: 11 · 2014: 13 · 2013: 11 · 2012: 17
- FWCI
- 20.63
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular Human Reproduction (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD-036887, U54HD040093, U54-HD40093, R01HD044715, HD 044715)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Endometriosis Research and Treatment
- Life Sciences › Immunology and Microbiology › Immunology › Reproductive System and Pregnancy
- Health Sciences › Medicine › Obstetrics and Gynecology › Gynecological conditions and treatments
- Keywords
- endometriosis, HOXA10, decidualization, eutopic endometrium, IGFBP-1, CD61, Emx2, DNA methylation, promoter methylation, endometrial stromal cells, baboon model, infertility, estradiol, medroxyprogesterone acetate, cyclic AMP
- MeSH terms
- Homeobox A10 Proteins, Empty Spiracles Homeobox Proteins, Animals, Cells, Cultured, Decidua, Bucladesine, Endometriosis, Endometrium, Epithelial Cells, Estradiol, Female, Gene Expression Regulation, Humans, Papio, Promoter Regions, Genetic, RNA, Messenger, Transcription Factors, Stromal Cells, Medroxyprogesterone Acetate, Homeodomain Proteins, Insulin-Like Growth Factor Binding Protein 1, DNA Methylation, Gene Silencing
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