{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T17:21:17Z","timestamp":1792084877918,"version":"4.4.0"},"reference-count":263,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,5,24]],"date-time":"2025-05-24T00:00:00Z","timestamp":1748044800000},"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>Socioeconomic factors have led an increasing number of women to postpone childbirth, thereby elevating the risks of reduced fertility, pregnancy complications, preterm birth, cesarean delivery, and chromosomal abnormalities. While diminished oocyte quality is a well-established contributor to age-related infertility, endometrial dysfunction also plays a pivotal role. Optimizing both oocyte quality and endometrial health is essential for enhancing reproductive outcomes. Although aging has been defined by twelve hallmarks, research specifically addressing age-related changes in endometrial function remains limited. This review examines the process of endometrial aging, with a particular emphasis on mitochondrial function. A comprehensive literature search was conducted using PubMed and Google Scholar to identify relevant studies published up to 31 January 2025. Endometrial aging is driven by multiple biological mechanisms, most notably the decline in endometrial receptivity. Key contributing factors include hormonal dysregulation, chronic inflammation, cell cycle arrest, genomic instability, epigenetic alterations, telomere attrition, and mitochondrial dysfunction. Among these, mitochondrial dysfunction emerges as a central driver of the aging process. Endometrial senescence, precipitated by irreversible mitochondrial impairment, may underlie the progressive decline in reproductive potential. Elucidating the role of mitochondrial dysfunction in aging provides critical insights into the molecular basis of fertility decline, particularly through its impact on endometrial receptivity.<\/jats:p>","DOI":"10.3390\/ijms26115060","type":"journal-article","created":{"date-parts":[[2025,5,25]],"date-time":"2025-05-25T20:26:50Z","timestamp":1748204810000},"page":"5060","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Endometrial Aging and Reproductive Decline: The Central Role of Mitochondrial Dysfunction"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8124-6269","authenticated-orcid":false,"given":"Hiroshi","family":"Kobayashi","sequence":"first","affiliation":[{"name":"Department of Gynecology and Reproductive Medicine, Ms. Clinic MayOne, 871-1 Shijo-cho, Kashihara 634-0813, Japan"},{"name":"Department of Obstetrics and Gynecology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8522, 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":"Hiroshi","family":"Shigetomi","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, Aska Ladies Clinic, 3-3-17 Kitatomigaoka-cho, Nara 634-0001, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shogo","family":"Imanaka","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Reproductive Medicine, Ms. Clinic MayOne, 871-1 Shijo-cho, Kashihara 634-0813, Japan"},{"name":"Department of Obstetrics and Gynecology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8522, 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"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"848","DOI":"10.1093\/humupd\/dmr026","article-title":"Why do people postpone parenthood? 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