{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T09:28:53Z","timestamp":1787218133744,"version":"build-2736575974"},"reference-count":72,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T00:00:00Z","timestamp":1787184000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Premature ovarian insufficiency (POI) is increasingly recognized as a disorder shaped not only by follicle-intrinsic defects but also by disruption of the ovarian tissue microenvironment. This Mini Review reframes POI as a process of inflammatory ovarian remodeling, in which immune activation, macrophage polarization, mitochondrial stress, inflammasome signaling, and inflammatory regulated cell death interact to accelerate follicular injury and ovarian reserve decline. Rather than providing a pathway-by-pathway summary, we highlight a stepwise model linking upstream genetic, iatrogenic, autoimmune, oxidative, and metabolic insults to immune-cell remodeling, granulosa cell dysfunction, oocyte damage, and follicular loss. Particular attention is given to the macrophage\u2013mitochondria\u2013NLRP3 axis and to the emerging role of pyroptosis and ferroptosis as amplifiers of ovarian inflammation. We also discuss how cell-based therapy, metabolic intervention, mitochondrial protection, inflammasome inhibition, and ferroptosis blockade may restore microenvironmental homeostasis. Finally, we emphasize that current evidence remains largely preclinical and that human samples, spatial omics, and longitudinal studies are needed to validate inflammatory remodeling programs across different POI subtypes.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1909202","type":"journal-article","created":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T09:19:47Z","timestamp":1787217587000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Inflammatory remodeling of the ovarian microenvironment in premature ovarian insufficiency: mechanisms and therapeutic opportunities"],"prefix":"10.3389","volume":"17","author":[{"given":"Jiao","family":"Fu","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Affiliated Hospital of Nantong University","place":["Nantong, China"]},{"name":"School of Medicine, Nantong University","place":["Nantong, Jiangsu, 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