The potential role of NLRP3 inflammasome in integrating redox, metabolic, and inflammatory signals during follicular development: a hypothesis-driven redox-metabolic integrator framework

Abstract

Follicular development is a complex and dynamic biological process involving coordinated interactions among endocrine regulation, cellular metabolism, redox homeostasis, mitochondrial function, and immune signaling. Increasing evidence indicates that oxidative stress, metabolic remodeling, and inflammatory responses are closely interconnected within the ovarian microenvironment and collectively influence follicular developmental outcomes. The NLRP3 inflammasome, traditionally recognized as an intracellular sensor of danger-associated signals, has recently emerged as an important mediator linking oxidative stress, mitochondrial dysfunction, metabolic disturbances, and inflammatory activation. Within ovarian tissues, NLRP3 activation has been associated with granulosa cell function, inflammatory remodeling, follicular atresia, ovulatory processes, and reproductive disorders. In this review, we summarize current knowledge regarding the regulation and functional implications of NLRP3 signaling during follicular development, with particular emphasis on its interactions with redox metabolism, mitochondrial homeostasis, and inflammatory pathways. Based on currently available evidence, we propose a hypothesis-driven framework in which NLRP3 may act as a candidate redox-metabolic integrative node that coordinates stress-related signals within the follicular microenvironment and may contribute to developmental transitions including follicular growth, dominance acquisition, ovulatory competence, and atresia. Importantly, this framework does not suggest that NLRP3 independently determines follicular fate. Rather, it provides a conceptual model describing how NLRP3-associated inflammatory signaling may interact with endocrine, metabolic, and redox networks to influence follicular developmental trajectories. The proposed framework remains to be validated through cell-specific genetic models, temporal intervention studies, and quantitative molecular profiling approaches. Understanding the potential integrative role of NLRP3 may provide new insights into the mechanisms underlying ovarian disorders, including polycystic ovary syndrome, primary ovarian insufficiency, and ovarian aging, while highlighting potential directions for future therapeutic exploration.