EndMT: New findings on the origin of myofibroblasts in endometrial fibrosis of intrauterine adhesions

Abstract

Background Intrauterine adhesion (IUA) is one of the leading causes of infertility and the main clinical challenge is the high recurrence rate. The key to solving this dilemma lies in elucidating the mechanisms of endometrial fibrosis. The aim of our team is to study the mechanism underlying intrauterine adhesion fibrosis and the origin of fibroblasts in the repair of endometrial fibrosis. Methods Our experimental study involving an animal model of intrauterine adhesion and detection of fibrosis-related molecules. The levels of molecular factors related to the endothelial-to-mesenchymal transition (EndMT) were examined in a rat model of intrauterine adhesion using immunofluorescence, immunohistochemistry, qPCR and Western blot analyses. Main outcome measures are levels of the endothelial marker CD31 and the mesenchymal markers alpha-smooth muscle actin (α-SMA) and vimentin. Results Immunofluorescence co-localization of CD31 and a-SMA showed that 14 days after moulding, double positive cells for CD31 and a-SMA could be clearly observed in the endometrium. Decreased CD31 levels and increased α-SMA and vimentin levels indicate that EndMT is involved in intrauterine adhesion fibrosis. Conclusions Endothelial cells promote the emergence of fibroblasts via the EndMT during the endometrial fibrosis of intrauterine adhesions.

Differential Staining Patterns for Evaluation of Ovarian and Oviducts Fibrosis Using the Polarized Light Microscope and the Digital Images Analysis

“…The current immunohistochemical findings revealed a significant increase of vimentin and α-SMA along with ovarian and oviduct fibrosis. Several studies considered vimentin and α-SMA as reliable fibrotic markers [42][43][44] . Mesenchymal myofibroblasts cells have an intermediate nature between fibroblasts and smooth muscle cells and they are the major cells responsible for the production of collagen, which leads to fibrosis.…”

“…Vimentin is strongly expressed in mesenchyme tissues, with weak to negative immunoexpression in epithelial cells, whereas α-SMA expression in the cytoplasm provides cellular contractility, which is intimately related with fibrosis [44] . Myofibroblasts generally vanish following effective tissue healing, but deregulation of normal repair mechanisms, such as chronic inflammation or oxidative stress in the tissue, can result in prolonged myofibroblasts activation leading to excess collagen production, which finally results in fibrosis [43] . The significant increase of hydroxyproline, a major component of collagen, in the presented work is in agreement with several studies that reported the correlation between fibrosis and hydroxyproline elevation [43,45] .…”

“…Myofibroblasts generally vanish following effective tissue healing, but deregulation of normal repair mechanisms, such as chronic inflammation or oxidative stress in the tissue, can result in prolonged myofibroblasts activation leading to excess collagen production, which finally results in fibrosis [43] . The significant increase of hydroxyproline, a major component of collagen, in the presented work is in agreement with several studies that reported the correlation between fibrosis and hydroxyproline elevation [43,45] . A Hydroxyproline value is a surrogate indicator of collagen regulation and metabolism.…”

Endometriosis, the Silent Disease: Molecular Targets, Active Principles, and Drug Delivery Systems

“…Fibroblasts are increasingly recognized as playing a role in inflammation, [62] implicating that fibrosis and inflammation are closely intertwined, potentially through macrophages [47] . The epithelial‐to‐mesenchymal transition, in which epithelial cells lose their intercellular junctions and become migratory and invasive, is known to play a role in endometriosis through fibroblast activation [63–66] . In other diseases, chronic low‐grade inflammation is recognized as a precursor to fibrosis [54] and this may also be the case for endometriosis.…”

Correction to: EndMT: New fndings on the origin of myofbroblasts in endometrial fbrosis of intrauterine adhesions

“…Correction to: Reprod Biol Endocrinol 20, 9 (2022) https://doi.org/10.1186/s12958-022-00887-5 Following publication of the original article [1], the authors reported an error in Fig. 1.…”