Follicular development impairment in polyendocrine metabolic ovarian syndrome: multidimensional pathophysiological networks and frontier therapeutic targets
- 1A Reproductive Medicine Center, The Affiliated Taizhou People’s Hospital of Nanjing Medical University, Taizhou School of Clinical Medicine, Nanjing Medical University
Abstract
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—including developmental epigenetic programming, the gut-brain-ovary axis, and circadian rhythms—ultimately establishing a pathologically entrenched state. Finally, this network-based understanding informs future research pathways, focusing on how emerging strategies—such as multi-omics integration, artificial intelligence, and stem cell secretome studies—can 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.
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BibTeX
@article{jia2026follicular,
title = {{Follicular development impairment in polyendocrine metabolic ovarian syndrome: multidimensional pathophysiological networks and frontier therapeutic targets}},
author = {Qiucheng Jia and Shuli Zhang and Lixin Zhang and Guangzong Zhao and Qi Zhu and Hongshan Ge},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1879713},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1879713/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Follicular development impairment in polyendocrine metabolic ovarian syndrome: multidimensional pathophysiological networks and frontier therapeutic targets
AU - Qiucheng Jia
AU - Shuli Zhang
AU - Lixin Zhang
AU - Guangzong Zhao
AU - Qi Zhu
AU - Hongshan Ge
PY - 2026
DA - 2026/10/07
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1879713
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1879713/full
AB - 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—including developmental epigenetic programming, the gut-brain-ovary axis, and circadian rhythms—ultimately establishing a pathologically entrenched state. Finally, this network-based understanding informs future research pathways, focusing on how emerging strategies—such as multi-omics integration, artificial intelligence, and stem cell secretome studies—can 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.
SN - 1664-3224
ER -