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

Carlos Patricio Alvarado-Díaz, Alvarado-Díaz CP, Marco T. Núñez, Marco Tulio Núñez, Núñez MT, Luigi Devoto, Devoto L, González-Ramos R, Reinaldo González-Ramos
Fertility and sterility · 2016 · vol. 106(2) , pp. 393–401 · doi:10.1016/j.fertnstert.2016.04.002 · PMID:27117373 · W2338730519
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This study investigated endometrial expression of the iron transporter DMT1 and its modulation in vitro, exploring implications for endometriosis pathology.

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Abstract

ObjectiveTo 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).DesignObservational and experimental study.SettingUniversity 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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Condition tags

endometriosis

MeSH descriptors

Cation Transport Proteins Endometriosis Endometrium Stromal Cells Apoferritins Apoferritins Biopsy Case-Control Studies Cation Transport Proteins Endometriosis Endometriosis Endometriosis Endometrium Endometrium Endometrium Endometrium Female Ferrous Compounds Ferrous Compounds Humans

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