Origin and Pathogenic Mechanisms of Uterine Adenomyosis: What Is Known So Far
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REVIEW
Origin and Pathogenic Mechanisms of Uterine Adenomyosis: What Is Known So Far Christina Anna Stratopoulou 1 & Jacques Donnez 2 & Marie-Madeleine Dolmans 1,3 Received: 16 August 2020 / Accepted: 11 October 2020 # Society for Reproductive Investigation 2020
Abstract Uterine adenomyosis is a benign disease, commonly encountered in reproductive-age women and responsible for chronic pelvic pain, abnormal uterine bleeding, and infertility. Although the exact origin and pathogenic mechanisms involved in adenomyosis still need to be elucidated, significant progress has been made over recent years. Ever since the theory of endometrium invaginating the myometrium via a traumatized interface was first proposed, numerous molecular mechanisms have been reported to participate in this process. At the same time, an alternative theory has suggested de novo development of adenomyotic lesions from metaplasia of Müllerian remnants or adult stem cells. Hence, our understanding of the pathogenesis of adenomyosis has been greatly enhanced and is anticipated to pave the way for development of an effective and safe treatment. The goal of this review is to analyze current knowledge on the origin and pathogenic mechanisms of adenomyosis, ranging from the most widely accepted theories to newly reported data. Keywords Adenomyosis . Pathogenesis . Invagination . Metaplasia . Disease mechanisms
Introduction Adenomyosis is a compound word, etymologically deriving from the Greek terms aδénas (αδένας), meaning gland, and mís (μυς), meaning muscle, and referring to a pathological condition of the muscle involving glands. Even though the term “adenomyosis uteri” dates back to 1925 [1], the current definition is largely based on a 1972 publication, when Bird et al. defined adenomyosis as “benign invasion of endometrium into the myometrium, producing a diffusely enlarged uterus which microscopically exhibits ectopic, non-neoplastic, endometrial glands and stroma surrounded by hypertrophic-hyperplastic musculature” [2]. Today, adenomyosis is commonly described
* Marie-Madeleine Dolmans [email protected] 1
Pôle de Recherche en Gynécologie, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, Brussels, Belgium
2
Société de Recherche pour l’Infertilité, Brussels, Belgium
3
Gynecology Department, Cliniques Universitaires Saint Luc, Brussels, Belgium
as an estrogen-dependent benign uterine disease, characterized by the presence of endometrial tissue penetrating the myometrium to a depth of at least 2.5 mm at the time of histological diagnosis, and often surrounded by hyperplastic and hypertrophic smooth muscle [3, 4]. Based on the distribution pattern of lesions inside the myometrium, adenomyosis is characterized as focal when a nodular collection is identified, or diffuse when glands and stroma are dispersed throughout the myometrium [3, 5]. Besides distinct histological patterns, these two forms of adenomyosis have been found to present with different degrees of symptoms, infertility, and a
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