The ferroimmunomodulatory role of ectopic endometriotic stromal cells in ovarian endometriosis

Immortalized ectopic endometriotic stromal cells produced complement C3 and pentraxin-3 as major secretory proteins in comparison to eutopic counterparts, and revealed different regulation in iron metabolism.


Hiroharu Kobayashi, M.D., Yoriko Yamashita, M.D., Ph.D., Akira Iwase, M.D., Ph.D., Yutaka Yoshikawa, Ph.D., Hiroyuki Yasui, Ph.D., Yoshichika Kawai, Ph.D., Koji Uchida, Ph.D., Nozomi Uno, Shinya Akatsuka, Ph.D., Takashi Takahashi, M.D., Ph.D., Fumitaka Kikkawa, M.D., Ph.D., Shinya Toyokuni, M.D., Ph.D.

Vol 98, Issue 2 , Pages 415-422.e12



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


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




Women with and without OEM.


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

Main Outcome Measure(s):

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.


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.


Immortalized ectopic endometriotic stromal cells in OEM predominantly secrete C3 and PTX3 and exhibit a differential regulation of iron metabolism.

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