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


METHODS
Observational and experimental study.


METHODS
University hospital research laboratory.


METHODS
Thirty-one healthy women and 24 endometriosis patients.


METHODS
Menstrual, proliferative, and secretory endometrial biopsies. Isolated ESCs from seven endometrial biopsies incubated with IL-1β or FeSO4 overload for 24 hours.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Instituto de Investigaciones Materno Infantil, Departamento de Obstetricia y Ginecología, Hospital San Borja-Arriarán, Facultad de Medicina, Universidad de Chile, Santiago, Chile.
Carlos Patricio
CP
Alvarado-Díaz
Instituto de Dinámica Celular y Biotecnología, Facultad de Ciencias, Universidad de Chile, Santiago, Chile.
Marco Tulio
MT
Núñez
Instituto de Investigaciones Materno Infantil, Departamento de Obstetricia y Ginecología, Hospital San Borja-Arriarán, Facultad de Medicina, Universidad de Chile, Santiago, Chile.
Luigi
L
Devoto
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.
Reinaldo
R
González-Ramos
D001052:Apoferritins / Q000378:metabolism; D001706:Biopsy; D016022:Case-Control Studies; D027682:Cation Transport Proteins / Q000378:metabolism*; D004715:Endometriosis / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D004717:Endometrium / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D005260:Female; D005296:Ferrous Compounds / Q000494:pharmacology; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism; D053583:Interleukin-1beta / Q000494:pharmacology; D019190:Iron Overload / Q000378:metabolism / Q000473:pathology; D008597:Menstrual Cycle; D018384:Oxidative Stress; D015398:Signal Transduction; D017154:Stromal Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D046509:Tissue Culture Techniques; D000099236:Solute Carrier Family 11, Member 2
D001052:Apoferritins; D027682:Cation Transport Proteins; D005296:Ferrous Compounds; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D000099236:Solute Carrier Family 11, Member 2; C507433:FTL protein, human; C508585:IL1B protein, human; C020748:ferrous sulfate
DMT1; endometriosis; interleukin-1β; iron