FKBP4 is regulated by HOXA10 during decidualization and in endometriosis
Open accessAbstract
FKBP4 (FKBP52) and FKBP5 (FKBP51) are progestin receptor (PR) co-chaperone proteins that enhance and inhibit, respectively, progestin-mediated transcription by PR. Here, we examined FKBP4 and FKBP5 expression in the eutopic endometrium of fertile women with endometriosis and effects of FKBP4 and FKBP5 on the decidualization of human endometrial stromal cells (HESCs), and assessed HOXA10 regulation of FKBP4. Expression of FKBP4 mRNA was increased in the late proliferative phase and remained elevated throughout the secretory phase. FKBP5 expression was low and remained constant throughout the menstrual cycle. Compared with controls, FKBP4 mRNA expression was decreased in the endometrium of women with endometriosis, whereas no significant endometriosis-related change was seen for FKBP5. Cultured HESCs were treated with either FKBP4 or FKBP5 siRNA and then decidualized by incubation with progesterone (P4) and 8-bromoadenosine cAMP. Treatment of HESCs with FKBP4 siRNA resulted in 60% lower IGFBP1 expression. In contrast, incubation with FKBP5 siRNA did not significantly decrease IGFBP1 expression during in vitro decidualization. HOXA10 and FKBP4 expression increased in parallel during in vitro decidualization. In HESCs, overexpressed HOXA10 enhanced FKBP4 mRNA and protein levels, whereas HOXA10 knockdown decreased FKBP4 mRNA and protein levels compared with controls. Similarly, during in vitro decidualization, FKBP4 expression was decreased in HOXA10-silenced cells. Enhanced HOXA10 expression in HESCs elicits a decidualization mediating increase in FKBP4 expression. The findings are consistent with the observation that women with endometriosis have diminished FKBP4 expression leading to impaired decidualization and infertility. The P4 resistance seen in endometriosis may be mediated through HOXA10-regulated FKBP4 expression.
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ENDOMETRIC FACTOR OF ENDOMETRIOSIS-ASSOCIATED INFERTILITY
Orazov, M. R., Radzinsky, V. E., Khamoshina, M. B., Владимировна, В. С., Abitova, M. Z., & Shustova, V. B. (2020) · Репродуктивная медицина · doi:10.37800/rm2020-1-22 · Cited by 2 · see citing works
Infectious and noninfectious endometritis and recurrent pregnancy loss
Kimura, F., Morimune, A., Nakamura, A., Kitazawa, J., Hanada, T., & Murakami, T. (2022) · Elsevier eBooks · doi:10.1016/b978-0-323-90805-4.00002-x
ANALISIS KEMURNIAN EKSTRAKSI ASAM RIBONUKLEAT PADA SAMPEL DARAH MENSTRUASI
Ocktariyana, O., Lestari, D. I., & Asmarinah, A. (2022) · JPP (Jurnal Kesehatan Poltekkes Palembang) · doi:10.36086/jpp.v17i2.1392
Wang, M., Xiang, Y., Zhang, D., Geng, X., Han, X., Guo, P., Zhang, L., & Tan, L. (2025) · Biology of Reproduction · doi:10.1093/biolre/ioaf126
- Authors
- Yang, H., Zhou, Y., Edelshain, B., Schatz, F., Lockwood, C. J., & Taylor, H. S.
- Affiliations
- Yale University (US)
- Corresponding author
- Taylor, Hugh S
- Venue
- Reproduction
- Publisher
- Oxford University Press (OUP)
- Published
- 2012-04-01
- Volume
- 143
- Issue
- 4
- Pages
- 531-538
- ISSN
- 1470-1626 (ISSN-L)
- 1741-7899
- OpenAlex
- W2169188211
- Cited by
- 63
- References
- 42
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 1 · 2023: 7 · 2022: 5 · 2021: 5 · 2020: 3 · 2019: 8 · 2018: 4 · 2017: 5 · 2016: 3 · 2015: 7 · 2014: 8 · 2013: 4 · 2012: 1
- FWCI
- 2.79
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Reproduction (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (NIH U54)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01 HD36887, U54 HD052688, R01HD036887)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Reproductive System and Pregnancy
- Health Sciences › Medicine › Reproductive Medicine › Endometriosis Research and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Keywords
- FKBP4, FKBP5, HOXA10, endometriosis, endometrial decidualization, endometrial stromal cells, progesterone resistance, IGFBP-1, menstrual cycle, infertility, transcriptional regulation
- MeSH terms
- Homeobox A10 Proteins, Tacrolimus Binding Protein 5, Adult, Animals, Cells, Cultured, Endometriosis, Female, Humans, Menstruation, Homeodomain Proteins, Insulin-Like Growth Factor Binding Protein 1, Tacrolimus Binding Proteins
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