Endometrial expression and in vitro modulation of the iron transporter divalent metal transporter 1 Implications for endometriosis

Authors:
Carlos Patricio Alvarado-Díaz, Ph.D., Marco Tulio Núñez, Ph.D., Luigi Devoto, M.D., Reinaldo González-Ramos, M.D., Ph.D.

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.

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