期刊
BIOLOGY OF REPRODUCTION
卷 91, 期 4, 页码 -出版社
SOC STUDY REPRODUCTION
DOI: 10.1095/biolreprod.114.119677
关键词
endometriosis; RBP1; retinoic acid
资金
- Eunice Kennedy Shriver National Institute of Child Health and Human Development/National Institutes of Health [R01HD55379, U01HD66439]
- National Institute of Allergy and Infectious Diseases [HHSN272202000046C]
- University of Maryland School of Pharmacy Mass Spectrometry Center [SOP1841-IQB2014]
- National Institutes of Health [DK090522, AA017927]
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 patientmatched 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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