Abstract
During the development of endometriosis, the presence of fibrotic tissues in and surrounding endometriotic lesions may lead to subsequent adhesion, anatomic distortion, and chronic pain. Therefore, studies aimed at clarifying the underlying mechanisms of fibrogenesis in endometriosis could potentially provide a novel strategy for effective treatment. Mesenchymal stem cells (MSCs) play a key role in fibrotic diseases by differentiating into myofibroblasts in appropriate microenvironment. In this study, we collected endometrial and endometriotic tissues from patients with endometriosis (n = 32) and control patients without endometriosis (n = 20) to compare the expression of fibrotic proteins and investigate the effect of endometriotic peritoneal fluid (PF) on myofibroblast differentiation of endometrial MSCs. We found that the expression of fibrotic proteins, including alpha-smooth muscle actin (α-SMA), type I collagen (collagen I), connective tissue growth factor (CTGF), and fibronectin, and the extent of fibrosis extremely enhanced in ectopic endometria compared with eutopic endometria from the same patients with endometriosis and normal endometria from patients without endometriosis. We next isolated and identified endometrial MSCs and found that treatment with endometriotic PF strongly induced endometrial MSCs to differentiate into myofibroblasts concomitant with the activation of Smad2/3. Moreover, ectopic endometrial MSCs expressed elevated collagen I, α-SMA, fibronectin, and CTGF. Sushi domain containing-2 (SUSD2), a marker of endometrial MSCs, and α-SMA, a well-recognized marker for myofibroblasts, colocalized extensively in ectopic endometria while seldom in normal and eutopic endometria. These findings suggest that ectopic endometrial MSCs are probably more susceptible to myofibroblast differentiation because of the long-term influence of endometriotic PF. All together, we report for the first time that endometriotic PF promotes myofibroblast differentiation of endometrial MSCs. This understanding will greatly improve our understanding of the pathophysiology of endometriosis and help design better therapeutics.
Highlights
Endometriosis, characterized by the presence of endometrial tissue outside the uterus, is a common gynecologic disease that affects 10% to 15% of all women and 35% to 50% of women with pelvic pain and/or infertility [1, 2]
Since activation of Smad2 or Smad3 plays an important role in myofibroblast differentiation [30], we examined whether endometriotic peritoneal fluid (PF) activated Smad2 or Smad3 in endometrial Mesenchymal stem cells (MSCs)
Endometrial MSCs from patients without endometriosis were treated with control or endometriotic PF, and the expression of collagen I, α-SMA, fibronectin, and connective tissue growth factor (CTGF) was examined by immunofluorescence analysis
Summary
Endometriosis, characterized by the presence of endometrial tissue outside the uterus, is a common gynecologic disease that affects 10% to 15% of all women and 35% to 50% of women with pelvic pain and/or infertility [1, 2]. The pathogenesis of endometriosis remains elusive, growing evidences have demonstrated that endometrium-derived mesenchymal stem cells (MSCs) and epithelial progenitors are crucial in the pathogenesis of endometriosis [12,13,14] It is considered as the main cause for endometriotic implants that endometrial MSCs and epithelial progenitors shed through the fallopian tube into the peritoneal cavity during menses [15]. Growth factors, and angiogenic factors are abnormally expressed in endometriotic peritoneal fluid (PF) [24] From this perspective, the different biological behaviors between ectopic and eutopic endometrial MSCs derived from the same patients [17] may result from the effects of endometriotic PF. We compared the expression of α-SMA, collagen I, CTGF, and fibronectin among normal, eutopic, and ectopic endometrial MSCs and detected the colocalization of the markers of endometrial MSCs and myofibroblasts in human endometriotic or endometrial tissues
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
