Retinoic Acid Biosynthesis Is Impaired in Human and Murine Endometriosis1
Open accessAbstract
Endometriosis is characterized by the presence of endometrial glands and stroma in extrauterine sites. Our objective was to determine whether endometriotic lesions (ELs) from women with endometriosis have altered retinoid levels compared with their eutopic endometrium, and to test the hypothesis that defects in all-trans retinoic acid (ATRA) biosynthesis in EL is related to reduced expression of cellular retinol-binding protein type 1 (RBP1). Retinoids were evaluated by liquid chromatography-tandem mass spectrometry and high-performance liquid chromatography in eutopic endometrial biopsies (EBs) and ELs from 42 patients with pathologically confirmed endometriosis. The ATRA levels were reduced, whereas the retinol and retinyl ester concentrations were elevated in EL compared with EB tissue. Similar results were found in a mouse model of endometriosis that used green fluorescent protein-positive endometrial tissue injected into the peritoneum of syngeneic hosts to mimic retrograde menses. The ATRA biosynthesis in vitro in retinol-treated primary human endometrial stromal cell (ESC) cultures derived from ELs was reduced compared with that of ESCs derived from patient-matched EBs. Correspondingly, RBP1 expression was reduced in tissue and ESCs derived from EL versus EB. Rbp1(-/-) mice showed reduced endometrial ATRA concentrations compared with wild type, associated with loss of tissue organization and hypercellularity. These findings provide the first quantitative measurements of ATRA in human endometrium and endometriosis, demonstrating reduced ATRA in ectopic tissue and corresponding ESC cultures. Quantitation of retinoids in murine endometriosis and in Rbp1(-/-) mice supports the contention that impaired ATRA synthesis caused by reduced RBP1 promotes an "endometriosis phenotype" that enables cells to implant and grow at ectopic sites.
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Impaired intracellular conversion of retinol to all-trans retinoic acid and deficiency of RBP1 contribute to decreased availability of retinoic acid.
“Impaired intracellular conversion of retinol to its active form, all-trans retinoic acid, and deficiency of retinol binding protein 1 (RBP1) also contribute to decreased availability of retinoic acid (Pavone et al., 2011;Pierzchalski et al., 2014).”
From Endometriosis and nuclear receptors (2019) · cites this paper as Pierzchalski et al., 2014
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- Authors
- Pierzchalski, K., Taylor, R. N., Nezhat, C., Jones, J. W., Napoli, J. L., Yang, G., Kane, M. A., & Sidell, N.
- Affiliations
- University of Maryland, Baltimore (US)
- Wake Forest University Health Sciences (US)
- Nezhat Medical Center (US)
- University of California, Berkeley (US)
- Emory University (US)
- Corresponding author
- Sidell, Neil
- ORCID
- Venue
- Biology of Reproduction
- Publisher
- Oxford University Press (OUP)
- Published
- 2014-10-01
- Volume
- 91
- Issue
- 4
- Pages
- 84-84
- ISSN
- 0006-3363 (ISSN-L)
- 1529-7268
- PMC
- PMC4435029
- OpenAlex
- W2167562037
- Cited by
- 50
- References
- 53
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 13 · 2023: 1 · 2022: 4 · 2021: 3 · 2020: 5 · 2019: 6 · 2018: 3 · 2017: 4 · 2016: 2 · 2015: 4
- FWCI
- 4.05
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Biology of Reproduction (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- BioOne Complete (BioOne) (submittedVersion)
- Funders
- National Institutes of Health
- U.S. Public Health Service (HHSN272202000046C)
- National Institute on Alcohol Abuse and Alcoholism (AA017927, R01AA017927)
- National Institute of Allergy and Infectious Diseases (HHSN272202000046C)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK090522, DK090522)
- National Institute of Child Health and Human Development
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01 HD 55379, U01HD066439, R01HD055379, U01 HD66439)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Endometriosis Research and Treatment
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Ectopic Pregnancy Diagnosis and Management
- Life Sciences › Immunology and Microbiology › Immunology › Reproductive System and Pregnancy
- Keywords
- endometriosis, retinoic acid synthesis, all-trans retinoic acid, CRBP1, retinoids, endometrial stromal cells, eutopic endometrium, ectopic endometrium, retrograde menstruation, endometriosis phenotypes
- MeSH terms
- Animals, Endometriosis, Female, Gene Expression Regulation, Humans, Species Specificity, Tretinoin, Mice, Knockout, Retinol-Binding Proteins, Cellular
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