Progesterone resistance in endometriosis is modulated by the altered expression of microRNA-29c and FKBP4
Open accessAbstract
Context: Endometriosis results in aberrant gene expression in the eutopic endometrium (EuE) and subsequent progesterone resistance. MicroRNA (miR) microarray data in a baboon model of endometriosis showed an increased expression of miR-29c. Objectives: To explore the role of miR-29c in progesterone resistance in a subset of women with endometriosis. Design: MiR-29c expression was analyzed in the endometrium of baboons and women with or without endometriosis. The role in progesterone resistance and decidualization was analyzed by transfecting human uterine fibroblast cells with miR-29c. Patients: Subjects diagnosed with deep infiltrative endometriosis (DIE) by transvaginal ultrasound with bowel preparation underwent surgical excision of endometriosis. Eutopic secretory endometrium was collected pre- and postoperatively. Women with normal EuE and without DIE served as controls. Results: Quantitative reverse transcription polymerase chain reaction demonstrated that miR-29c expression increased, while the transcript levels of its target, FK506-binding protein 4 (FKBP4), decreased in the EuE of baboons following the induction of endometriosis. FKBP4 messenger RNA and decidual markers were statistically significantly decreased in decidualized human uterine fibroblast cells transfected with a miR-29c mimic compared with controls. Human data corroborated our baboon data and demonstrated higher expression of miR-29c in endometriosis EuE compared with normal EuE. MiR-29c was significantly decreased in endometriosis EuE postoperatively compared with preoperative tissues, and FKBP4 showed an inverse trend following radical laparoscopic resection surgery. Conclusions: We demonstrate that miR-29c expression is increased in EuE of baboons and women with endometriosis, which might contribute to a compromised progesterone response by diminishing the levels of FKBP4. Resection of DIE is likely to reverse the progesterone resistance associated with endometriosis in women.
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Joshi et al. demonstrated in a nonhuman primate model of endometriosis the functional implication of increased expression of miR-29c in endometrial progesterone resistance.
“In addition, Joshi et al. recently demonstrated, in a nonhuman primate model of endometriosis, the functional implication of increased expression of miR-29c in endometrial progesterone resistance (108).”
From Biomarkers in endometriosis: Challenges and opportunities (2017) · cites this paper as [108]
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References 55 · Cited by 87
Research works printed but not linked: 2
- Giudice LC. Clinical practice: endometriosis. N Engl J Med. 2010; 362(25):2389-2398.
- Bulun SE. Endometriosis. N Engl J Med. 2009;360(3):268-279.
- Authors
- Joshi, N. R., Miyadahira, E. H., Afshar, Y., Jeong, J.-W., Young, S. L., Lessey, B. A., Serafini, P. C., & Fazleabas, A. T.
- Affiliations
- Michigan State University (US)
- University of California, Los Angeles (US)
- University of North Carolina at Chapel Hill (US)
- Prisma Health (US)
- Universidade de São Paulo (BR)
- ORCID
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2016-10-25
- Volume
- 102
- Issue
- 1
- Pages
- jc.2016-2076
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- PMC
- PMC5413101
- OpenAlex
- W2534032587
- Cited by
- 87
- References
- 55
- Citations by year
- 2026: 2 · 2025: 7 · 2024: 8 · 2023: 13 · 2022: 6 · 2021: 12 · 2020: 16 · 2019: 8 · 2018: 10 · 2017: 4 · 2015: 1
- FWCI
- 9.75
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
- UNC Libraries
- Funders
- Michigan State University
- National Institutes of Health
- College of Engineering, Michigan State University
- College of Human Medicine, Michigan State University
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD067721, R01HD083273)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Endometriosis Research and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Life Sciences › Immunology and Microbiology › Immunology › Reproductive System and Pregnancy
- Keywords
- endometriosis, progesterone resistance, microRNA-29c, FKBP4, eutopic endometrium, decidualization, deep infiltrating endometriosis, baboon model, laparoscopic resection, progesterone response
- MeSH terms
- Animals, Disease Models, Animal, Endometriosis, Endometrium, Female, Humans, Papio, Progesterone, Prognosis, Uterine Diseases, Biomarkers, Case-Control Studies, Tacrolimus Binding Proteins, MicroRNAs
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