Endometrial expression and in vitro modulation of the iron transporter divalent metal transporter-1: implications for endometriosis

• Published in: Fertility and sterility Vol. 106; no. 2; pp. 393 - 401
• Main Authors: Alvarado-Díaz, Carlos Patricio, Ph.D, Núñez, Marco Tulio, Ph.D, Devoto, Luigi, M.D, González-Ramos, Reinaldo, M.D., Ph.D
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.08.2016
• Subjects: Apoferritins - metabolism; Biopsy; Case-Control Studies; Cation Transport Proteins - metabolism; DMT1; endometriosis; Endometriosis - metabolism; Endometriosis - pathology; Endometriosis - physiopathology; Endometrium - drug effects; Endometrium - metabolism; Endometrium - pathology; Endometrium - physiopathology; Female; Ferrous Compounds - pharmacology; Humans; Inflammation - metabolism; Inflammation - pathology; Inflammation Mediators - metabolism; Interleukin-1beta - pharmacology; interleukin-1β; Internal Medicine; iron; Iron Overload - metabolism; Iron Overload - pathology; Menstrual Cycle; Obstetrics and Gynecology; Oxidative Stress; Signal Transduction; Stromal Cells - drug effects; Stromal Cells - metabolism; Stromal Cells - pathology; Tissue Culture Techniques; endometriosis; iron; DMT1; interleukin-1β
• ISSN: 0015-0282; 1556-5653
• DOI: 10.1016/j.fertnstert.2016.04.002

Objective To evaluate divalent metal transporter-1 (DMT1) expression in healthy women's and endometriosis patients' endometrium and to analyze DMT1 and ferritin light chain (Fn-L) expression modulation by iron overload and IL-1β in endometrial stromal cells (ESCs). Design Observational and experimental study. Setting University hospital research laboratory. Patient(s) Thirty-one healthy women and 24 endometriosis patients. Intervention(s) Menstrual, proliferative, and secretory endometrial biopsies. Isolated ESCs from seven endometrial biopsies incubated with IL-1β or FeSO4 overload for 24 hours. Main Outcome Measure(s) Divalent metal transporter-1 endometrial protein expression assessed by immunohistochemistry and Western blot. Divalent metal transporter-1 and Fn-L proteins expression in stimulated ESCs evaluated by Western blot. Result(s) Divalent metal transporter-1 is expressed throughout the menstrual cycle in human endometrium. Four endometrial DMT1 variants were identified accordingly to their molecular weight: DMT-80, -65, -55, and -50. Endometrial expression of DMT-80 and -55 is higher in endometriosis patients than in healthy women. In ESCs, iron overload induces an overexpression of DMT-80, DMT-50, and Fn-L, whereas IL-1β increases DMT-80 and -50 expressions and decreases Fn-L expression. Conclusion(s) Divalent metal transporter-1 overexpression in endometriosis patients’ endometrium can increase iron influx to endometrial cells, inducing oxidative stress–mediated proinflammatory signaling. In turn, endometriosis-related conditions, as iron overload and inflammation (IL-1β), enhance endometriosis patients endometrial DMT1 expression, creating a vicious circle on DMT-1–modulated pathways.