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

Some divalent metal transporter-1 variants are overexpressed in endometriosis patients’ endometrium. Divalent metal transporter-1 is upregulated by interleukin-1b and iron overload in endometrial stromal cells in vitro. These findings involve divalent metal transporter-1 on endometriosis pathophysiology.

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Volume 106, Issue 2, Pages 393-401

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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Fertility and Sterility

Editorial Office, American Society for Reproductive Medicine

Fertility and Sterility® is an international journal for obstetricians, gynecologists, reproductive endocrinologists, urologists, basic scientists and others who treat and investigate problems of infertility and human reproductive disorders.