The ferroimmunomodulatory role of ectopic endometriotic stromal cells in ovarian endometriosis.
OBJECTIVE
To understand the role of ectopic endometriotic stromal cells in ovarian endometriosis (OEM) and the associated risks for infertility and carcinogenesis.


METHODS
Analyses of secreted proteins and gene expression using immortalized eutopic/ectopic endometrial(-otic) stromal cells from OEM.


METHODS
University.


METHODS
Women with and without OEM.


METHODS
Samples of endometrial(-otic) tissue from women with or without OEM.


METHODS
Immunohistochemical analysis of oxidative stress in OEM, gene expression profiles, and the identification of secreted proteins by mass spectrometry in immortalized endometrial(-otic) stromal cells.


RESULTS
4-Hydroxy-2-nonenal-modified proteins and carboxymethyllysine were abundant in the stroma, rather than epithelia, of OEM patients, indicating the presence of oxidative stress. Immortalized ectopic endometriotic stromal cells exhibited high IRP1/IRP2/HIF-1β expression and contained lower amounts of iron and copper than their eutopic counterparts. Expression profiles, in combination with protein identification, revealed that complement component 3 (C3) and pentraxin-3 (PTX3) are the major proteins secreted from immortalized ectopic endometriotic stromal cells. Complement-3/PTX3 promoted the secretion of various cytokines by THP1 macrophage cells and thus supported M1 differentiation.


CONCLUSIONS
Immortalized ectopic endometriotic stromal cells in OEM predominantly secrete C3 and PTX3 and exhibit a differential regulation of iron metabolism.
Department of Pathology and Biological Responses, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya, Japan.
Hiroharu
H
Kobayashi
Yoriko
Y
Yamashita
Akira
A
Iwase
Yutaka
Y
Yoshikawa
Hiroyuki
H
Yasui
Yoshichika
Y
Kawai
Koji
K
Uchida
Nozomi
N
Uno
Shinya
S
Akatsuka
Takashi
T
Takahashi
Fumitaka
F
Kikkawa
Shinya
S
Toyokuni
D002097:C-Reactive Protein / Q000502:physiology; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D002828:Choristoma / Q000378:metabolism* / Q000473:pathology; D003176:Complement C3 / Q000502:physiology; D004715:Endometriosis / Q000378:metabolism* / Q000473:pathology; D004717:Endometrium / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D005260:Female; D006801:Humans; D056747:Immunomodulation / Q000502:physiology*; D007501:Iron / Q000276:immunology / Q000378:metabolism*; D010053:Ovary / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D000683:Serum Amyloid P-Component / Q000502:physiology; D017154:Stromal Cells / Q000378:metabolism; D000099153:Pentraxins
D002097:C-Reactive Protein; D003176:Complement C3; D007501:Iron; D000683:Serum Amyloid P-Component; D000099153:Pentraxins