Three-dimensional characterization of adenomyosis in female mice: Toward a novel system for drug efficacy evaluation

Abstract Adenomyosis is an intractable gynecological disorder that can give rise to severe pelvic pain, Heavy menstrual bleeding, and infertility, predominantly affecting women of reproductive age. The limited efficacy of current pharmacological interventions in certain cases—particularly those resistant to hormone therapies—underscores the urgent need for deeper mechanistic insights and the development of novel therapeutic strategies. Progress in this field, however, has been hampered by the scarcity of suitable experimental models, as adenomyosis is primarily a human disease. In this study, we demonstrate a preclinical platform for therapeutic evaluation using a mouse model of mechanically-induced adenomyosis, which recapitulates the key pathological features observed in humans. By integrating high-resolution three-dimensional (3D) tissue imaging, we successfully visualized the invagination and expansion of adenomyosis lesions spatiotemporally. This approach enabled the clear-cut and efficient assessment of progestin efficacy in situ. We propose that the combination of a mechanistically relevant mouse model and advanced 3D histological analysis constitutes a concise and robust system for therapeutic validation and compound screening, thereby facilitating the discovery of effective treatments for adenomyosis.