Endometrial Inflammation and Impaired Spontaneous Decidualization: Insights into the Pathogenesis of Adenomyosis

Abstract

Adenomyosis is an estrogen-dependent gynecologic disease characterized by the myometrial invasion of the endometrial tissue. This review summarized the current understanding and recent findings on the pathophysiology of adenomyosis, focusing on repeated menstruation, persistent inflammation, and impaired spontaneous decidualization. A literature search was performed in the PubMed and Google Scholar databases from inception to 30 April 2022. Thirty-one full-text articles met the eligibility criteria. Repeated episodes of physiological events (i.e., endometrial shedding, damage, proliferation, differentiation, repair, and regeneration) during the menstrual cycle are associated with inflammation, angiogenesis, and immune processes. The decidualization process in humans is driven by the rise in progesterone levels, independently of pregnancy (i.e., spontaneous decidualization). Adenomyotic cells produce angiogenic and fibrogenic factors with the downregulation of decidualization-associated molecules. This decidualization dysfunction and persistent inflammation are closely related to the pathogenesis of adenomyosis. Recently, it has been found that the reproductive tract microbiota composition and function in women with adenomyosis differ from those without. An increase in opportunistic pathogens and a decrease in beneficial commensals may promote impaired defense mechanisms against inflammation and predispose women to uncontrolled endometrial inflammation. However, currently, there is no direct evidence that adenomyosis is linked to pre-existing inflammation and impaired spontaneous decidualization. Overall, persistent inflammation, impaired spontaneous decidualization, and microbiota dysbiosis (i.e., an imbalance in the composition and function of endometrial microbiota) may be involved in the pathophysiology of adenomyosis.