From Elegance to Complexity: The Intricate Dance of Myometrial Stem Cells Transforming into Leiomyoma Stem Cells: Unraveling the Symphony of Genetic and Epigenetic Refinement

Abstract

Uterine leiomyomas (LM), commonly referred to as uterine fibroids (UFs), pelvic tumor in women of reproductive age globally and are main indicators of hysterectomies if become symptomatic. The progression of uterine LM involves a complex interplay of hormones, stem cells, growth factors, and genetic/epigenetic irregularities. Both endometrial and myometrial stem/progenitor cells play pivotal roles in the uterus’ response to hormonal stimuli and return to its basal state. LM, arising from a single stem cell of smooth muscle cells with acquired mutations, exhibit diverse cellular transcriptomic patterns influenced by genotype. Affecting over 70% of women at some point in their lives, with significant clinical symptoms, such as pelvic pain, infertility, and heavy uterine bleeding. Recent literature underscores the potential importance of LM stem cells and their paracrine interactions with specialized cells, connecting the gap between medications targeting leiomyoma expansion and potential eradication strategies. Keeping these points in view, this review discusses the current understanding of the involvement of myometrial stem/progenitor cells and the genetic and epigenetic changes occurring in these cells during the pathogenesis of uterine LM.