Possible involvement of inflammatory/reparative processes in the development of uterine fibroids

Abstract

Uterine leiomyomas are benign tumors in the smooth muscle layer of the uterus. The most common histological type is the "usual leiomyoma", characterized by overexpression of ECM proteins, whereas the "cellular type" has higher cellular content. Our objective is to investigate the involvement of inflammatory and reparative processes in leiomyoma pathobiology. Using a morphological approach, we investigate the presence of inflammatory cells. Next, we determine the localization of the ECM, the presence/absence of fibrotic cells via α-sma and desmin and the immunohistochemical profile of the mesenchymal cells with respect to CD34. Finally, we explore the effect of inflammatory mediators (TNF-α, IL-1β, IL-6, IL-15, GM-CSF and IFN-γ) on pro-fibrotic factor activin A mRNA expression in vitro. Higher numbers of macrophages were found inside and close to leiomyomas as compared to the more distant myometrium. Cellular leiomyomas showed more macrophages and mast cells than the "usual type". Inside the fibroid tissue, we found cells positive for α-sma, but negative for desmin and a large amount of collagen surrounding the nodule, suggestive of myofibroblasts producing ECM. In the myometrium and leiomyomas of the "usual type", we identified numerous CD34+ fibroblasts, which are known to give rise to myofibroblasts upon loss of CD34 expression. In leiomyomas of the "cellular type", stromal fibroblasts were CD34-negative. Finally, we found that TNF-α increased activin A mRNA in myometrial and leiomyoma cells. In conclusion, this study demonstrates the presence of inflammatory cells in uterine leiomyomas, which may contribute to excessive ECM production, tissue remodeling and leiomyoma growth.

Omega‐3 fatty acids modulate the lipid profile, membrane architecture, and gene expression of leiomyoma cells

“…To date, genetic and epigenetic factors, sex steroids, growth factors, cytokines, chemokines, inflammation, and extracellular matrix (ECM) components are known factors involved in the pathogenesis of leiomyoma (Ciarmela et al, ; Gallagher & Morton, ; Islam, Akhtar, Segars, Castellucci, & Ciarmela, ; Islam et al, ; Protic et al, ; Yang, Mas, Diamond, & Al‐Hendy, ). ECM components, mainly collagen1A1, fibronectin and versican are overexpressed in leiomyoma (Malik & Catherino, ), and their upregulation is induced by activin A (Islam et al, ).…”

The Emerging Spectrum of Early Life Exposure-Related Inflammation and Epigenetic Therapy

“…In addition, the defect of DNA repair response was recently observed in UFSCs [51]. In UFs, a recent study shows that higher numbers of macrophages are present inside and close to UFs as compared to the more distant myometrium [52]. Notably, several key pro-inflammatory mediators including IL-11, IL-13 and TGF-beta are overexpressed in UFs.…”

Uterine fibroids and risk of hypertension: Implication of inflammation and a possible role of the renin‐angiotensin‐aldosterone system

“…Uterine fibroids are benign tumors of the muscle layer of uterus, affecting about 70% of women by age 50 years, even if only 30% of patients are symptomatic and request treatment . UF can be considered a fibrotic disease starting with an invasion of inflammatory cells at the level of the uterus or alternatively by an increase of resident fibrotic cells . It is well known that the female genital tract is less reactive to inflammation and autoimmunity and this pattern allows spermatozoa to exert their reproductive function still maintaining a full protection against microbial invasion.…”