{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T01:33:32Z","timestamp":1790300012523,"version":"4.1.0"},"reference-count":125,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,6,20]],"date-time":"2025-06-20T00:00:00Z","timestamp":1750377600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"ANID","award":["FONDAP 152220002 (CECAN)"],"award-info":[{"award-number":["FONDAP 152220002 (CECAN)"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Ovarian cancer (OC) is the most lethal gynecological cancer globally. Its incidence and mortality consistently rise after menopause. While parity reduces the risk of OC, nulliparity during a woman\u2019s fertile years increases it. Although the association between reproductive history and OC risk is well-established, the long-term impact of pregnancy on the postmenopausal human ovary has received little to no attention. Parity apparently delays the natural decline of the ovarian reserve, but this association also remains unexplored to date. Based on data from cellular, biochemical, and histological markers, as well as epidemiological studies, transcriptomic analyses, and gene knockout mouse models, we review compelling evidence suggesting a critical intraovarian interplay between the residual ovarian reserve and the ovarian surface epithelium (OSE) in the aged ovary. This interaction appears to be a key factor underlying the protective effect of parity on ovarian cancer (OC) risk. We propose that functional FSHR signaling in the remnant follicles of the aged multiparous ovary somehow counteracts the oxidative stress and subsequent chronic inflammation typically observed in the senescent ovary. This mechanism would minimize DNA damage, thereby lowering the probability of neoplastic transformation in the aged mammalian ovary. The precise mechanism by which pregnancy imprints such a long-term follicle\u2013OSE crosstalk warrants further investigation.<\/jats:p>","DOI":"10.3390\/antiox14070759","type":"journal-article","created":{"date-parts":[[2025,6,20]],"date-time":"2025-06-20T06:10:27Z","timestamp":1750399827000},"page":"759","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Oxidative Stress, Parity History, and Remnant Follicles in the Aged Ovary: Insights on Ovarian Cancer Risk and Protection"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0522-5754","authenticated-orcid":false,"given":"Ulises","family":"Urz\u00faa","sequence":"first","affiliation":[{"name":"Laboratorio de Gen\u00f3mica Aplicada, Departamento de Oncolog\u00eda B\u00e1sico Cl\u00ednica, Facultad de Medicina, Universidad de Chile, Independencia 1027, Santiago 8380453, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3819-0973","authenticated-orcid":false,"given":"Arnaldo","family":"Mar\u00edn","sequence":"additional","affiliation":[{"name":"Laboratorio de Gen\u00f3mica del C\u00e1ncer, Departamento de Oncolog\u00eda B\u00e1sico Cl\u00ednica, Facultad de Medicina, Universidad de Chile, Independencia 1027, Santiago 8380453, Chile"},{"name":"Center for Cancer Prevention and Control (CECAN), Santiago 8331150, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3770-8550","authenticated-orcid":false,"given":"Enrique A.","family":"Castell\u00f3n","sequence":"additional","affiliation":[{"name":"Center for Cancer Prevention and Control (CECAN), Santiago 8331150, Chile"},{"name":"Laboratorio de Oncolog\u00eda Celular y Molecular, Departamento de Oncolog\u00eda B\u00e1sico Cl\u00ednica, Facultad de Medicina, Universidad de Chile, Independencia 1027, Santiago 8380453, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1038\/s41571-024-00881-3","article-title":"Global epidemiology of epithelial ovarian cancer","volume":"21","author":"Webb","year":"2024","journal-title":"Nat. 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