{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T13:55:44Z","timestamp":1791381344532,"version":"4.3.3"},"reference-count":170,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:00Z","timestamp":1791331200000},"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>Polyendocrine metabolic ovarian syndrome (PMOS) is a prevalent endocrine-metabolic disorder characterised by follicular arrest, anovulation, and elevated androgen levels. This review transcends single-dimensional analyses of PMOS pathology from neuroendocrine or metabolic perspectives, proposing an integrated multi-layered network model to systematically elucidate the pathological mechanisms underlying follicular arrest. Post-pubertal dysfunction of the hypothalamic-pituitary-ovarian axis interacts with systemic metabolic dysregulation, jointly establishing an ovarian microenvironment characterised by hyperandrogenism, hyperinsulinaemia, and chronic inflammation. This environment further induces self-reinforcing vicious cycles within follicles, manifesting as impaired granulosa-oocyte communication, immunometabolic reprogramming (e.g., M1 macrophage polarisation), and organelle stress (including mitochondrial dysfunction and endoplasmic reticulum stress). This localised cycle is consolidated and amplified by higher-level regulatory factors\u2014including developmental epigenetic programming, the gut-brain-ovary axis, and circadian rhythms\u2014ultimately establishing a pathologically entrenched state. Finally, this network-based understanding informs future research pathways, focusing on how emerging strategies\u2014such as multi-omics integration, artificial intelligence, and stem cell secretome studies\u2014can advance phenotype-directed precision interventions. This review aims to provide a systematic, dynamic theoretical framework for understanding the complex pathogenesis of PMOS and its potential therapeutic targets.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1879713","type":"journal-article","created":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T13:21:45Z","timestamp":1791379305000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Follicular development impairment in polyendocrine metabolic ovarian syndrome: multidimensional pathophysiological networks and frontier therapeutic targets"],"prefix":"10.3389","volume":"17","author":[{"given":"Qiucheng","family":"Jia","sequence":"first","affiliation":[{"name":"A Reproductive Medicine Center, The Affiliated Taizhou People\u2019s Hospital of Nanjing Medical University, Taizhou School of Clinical Medicine, Nanjing Medical University","place":["Taizhou, 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