{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T23:45:02Z","timestamp":1792799102578,"version":"4.5.0"},"reference-count":178,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2025,9,18]],"date-time":"2025-09-18T00:00:00Z","timestamp":1758153600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Endometriosis is a chronic disease characterized by the ectopic presence of endometrial cells that evade apoptosis and survive and proliferate under harsh environmental conditions. It is closely associated with infertility and pregnancy-related complications. This review focuses on the molecular pathophysiology of endometriosis, particularly the disruption of the p53\u2013AMPK\u2013mTOR signaling axis, and highlights the dysregulation of decidualization and cellular senescence, incorporating recent findings in reproductive physiology. A comprehensive literature search was conducted using PubMed and Google Scholar without temporal restrictions. Endometriotic cells adapt to the hostile peritoneal environment through resistance to apoptosis and alterations in autophagy. In the early stages, autophagy activation may promote cell survival; however, as the disease progresses, autophagic activity tends to decline. Aberrant activation of mTOR signaling is implicated in this process, contributing to the suppression of autophagy, impaired decidualization, and promotion of cellular senescence, ultimately facilitating lesion progression and infertility. Indeed, in the eutopic endometrium of patients with endometriosis, progesterone resistance, elevated inflammatory cytokines, and epigenetic abnormalities are known to reduce endometrial receptivity. Moreover, suppression of autophagy leads to excessive cellular senescence and secretion of the senescence-associated secretory phenotype (SASP), thereby interfering with proper decidualization. Maintaining an appropriate balance between decidualization and cellular senescence is essential for reproductive function. Future development of therapeutic strategies targeting these processes is expected to help overcome infertility associated with endometriosis.<\/jats:p>","DOI":"10.3390\/ijms26189125","type":"journal-article","created":{"date-parts":[[2025,9,18]],"date-time":"2025-09-18T14:45:46Z","timestamp":1758206746000},"page":"9125","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Balancing Decidualization, Autophagy, and Cellular Senescence for Reproductive Success in Endometriosis Biology"],"prefix":"10.3390","volume":"26","author":[{"given":"Hiroshi","family":"Shigetomi","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8522, Japan"},{"name":"Department of Gynecology and Reproductive Medicine, Aska Ladies Clinic, 3-3-17 Kitatomigaoka-cho, Nara 634-0001, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miki","family":"Nishio","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Reproductive Medicine, Ms.Clinic MayOne, 871-1 Shijo-cho, Kashihara 634-0813, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mai","family":"Umetani","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Reproductive Medicine, Ms.Clinic MayOne, 871-1 Shijo-cho, Kashihara 634-0813, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shogo","family":"Imanaka","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8522, Japan"},{"name":"Department of Gynecology and Reproductive Medicine, Ms.Clinic MayOne, 871-1 Shijo-cho, Kashihara 634-0813, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiratsugu","family":"Hashimoto","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Reproductive Medicine, Ms.Clinic MayOne, 871-1 Shijo-cho, Kashihara 634-0813, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8124-6269","authenticated-orcid":false,"given":"Hiroshi","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8522, Japan"},{"name":"Department of Gynecology and Reproductive Medicine, Ms.Clinic MayOne, 871-1 Shijo-cho, Kashihara 634-0813, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1244","DOI":"10.1056\/NEJMra1810764","article-title":"Endometriosis","volume":"382","author":"Zondervan","year":"2020","journal-title":"N. 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