Macrophages and immunometabolism in diminished ovarian reserve: pathological features and therapeutic implications.
- 1Gansu University of Chinese Medicine, Clinical School of Traditional Chinese Medicine, Lanzhou, China.
Abstract
Diminished ovarian reserve (DOR) is a prevalent reproductive endocrine disorder that significantly impairs female fertility. While traditional research has emphasized intrinsic oocyte defects, growing evidence highlights the ovarian immune microenvironment-specifically macrophages-as a critical regulator of follicular fate and reserve maintenance. Nevertheless, the mechanisms by which macrophage dysfunction drives DOR remain incompletely understood, and the interplay between chronic inflammation and macrophage metabolic reprogramming has yet to be systematically elucidated. This narrative review synthesizes literature from immunology, metabolism, and reproductive medicine, framing current evidence as established findings, putative mechanisms, and emerging hypotheses. The key findings are threefold: 1) macrophage polarization imbalance, which is marked by sustained M1 activation and impaired M2 function, constitutes a core pathological feature of DOR; 2) this imbalance is driven by metabolic reprogramming-specifically, metabolic inflexibility in M1 (persistent glycolytic commitment) and suppressed oxidative phosphorylation in M2-which links inflammaging to ovarian fibrosis and follicular depletion; and 3) pharmacological modulation of macrophage immunometabolism (e.g., AMPK/PPARγ activators, LXR agonists, and itaconate) and engineered delivery platforms (e.g., exosomes and targeted nanocarriers) hold preclinical promise. This review establishes an "immunometabolic axis" framework that integrates macrophage polarization, metabolic dysregulation, and ovarian reserve loss, advancing the understanding of DOR pathogenesis and informing precision interventions.
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BibTeX
@article{li2026macrophages,
title = {{Macrophages and immunometabolism in diminished ovarian reserve: pathological features and therapeutic implications.}},
author = {Bingxia Li and Jia Zhang and Quansheng Wu and Xiaohua Zhang},
journal = {Frontiers in endocrinology},
year = {2026},
month = oct,
doi = {10.3389/fendo.2026.1883984},
url = {https://europepmc.org/article/MED/42899025},
note = {CC BY},
}
RIS
TY - JOUR
TI - Macrophages and immunometabolism in diminished ovarian reserve: pathological features and therapeutic implications.
AU - Bingxia Li
AU - Jia Zhang
AU - Quansheng Wu
AU - Xiaohua Zhang
PY - 2026
DA - 2026/10/05
JO - Frontiers in endocrinology
DO - 10.3389/fendo.2026.1883984
UR - https://europepmc.org/article/MED/42899025
AB - Diminished ovarian reserve (DOR) is a prevalent reproductive endocrine disorder that significantly impairs female fertility. While traditional research has emphasized intrinsic oocyte defects, growing evidence highlights the ovarian immune microenvironment-specifically macrophages-as a critical regulator of follicular fate and reserve maintenance. Nevertheless, the mechanisms by which macrophage dysfunction drives DOR remain incompletely understood, and the interplay between chronic inflammation and macrophage metabolic reprogramming has yet to be systematically elucidated. This narrative review synthesizes literature from immunology, metabolism, and reproductive medicine, framing current evidence as established findings, putative mechanisms, and emerging hypotheses. The key findings are threefold: 1) macrophage polarization imbalance, which is marked by sustained M1 activation and impaired M2 function, constitutes a core pathological feature of DOR; 2) this imbalance is driven by metabolic reprogramming-specifically, metabolic inflexibility in M1 (persistent glycolytic commitment) and suppressed oxidative phosphorylation in M2-which links inflammaging to ovarian fibrosis and follicular depletion; and 3) pharmacological modulation of macrophage immunometabolism (e.g., AMPK/PPARγ activators, LXR agonists, and itaconate) and engineered delivery platforms (e.g., exosomes and targeted nanocarriers) hold preclinical promise. This review establishes an "immunometabolic axis" framework that integrates macrophage polarization, metabolic dysregulation, and ovarian reserve loss, advancing the understanding of DOR pathogenesis and informing precision interventions.
SN - 1664-2392
ER -