Carlos Patricio Alvarado-Díaz1, Marco Tulio Núñez2, Luigi Devoto1, Reinaldo González-Ramos3. 1. Instituto de Investigaciones Materno Infantil, Departamento de Obstetricia y Ginecología, Hospital San Borja-Arriarán, Facultad de Medicina, Universidad de Chile, Santiago, Chile. 2. Instituto de Dinámica Celular y Biotecnología, Facultad de Ciencias, Universidad de Chile, Santiago, Chile. 3. Instituto de Investigaciones Materno Infantil, Departamento de Obstetricia y Ginecología, Hospital San Borja-Arriarán, Facultad de Medicina, Universidad de Chile, Santiago, Chile. Electronic address: rgonzalezr@med.uchile.cl.
Abstract
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.
OBJECTIVE: To evaluate divalent metal transporter-1 (DMT1) expression in healthy women's and endometriosispatients' 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 endometriosispatients. 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 endometriosispatients 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 endometriosispatients' 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 endometriosispatients endometrial DMT1 expression, creating a vicious circle on DMT-1-modulated pathways.