The immune microenvironment: a key regulator of ovarian function during ovarian aging

The ovary is a highly dynamic organ characterized by intense biosynthetic activity, cyclical tissue remodeling, and elevated metabolic flux. Within this demanding milieu, precise immune regulation is paramount: tightly coordinated tissue remodeling by innate immunity and vigilant immune surveillance by the adaptive system are critical for maintaining ovarian homeostasis. Mounting evidence identifies dysregulation of the local ovarian immune microenvironment as a core driver of functional decline. This review synthesizes current knowledge on how the ovarian immune microenvironment, in concert with endocrine signals, orchestrates key phases of oocyte development and follicular maturation. We then delineate the immune signatures underpinning physiological ovarian aging and pathological premature ovarian insufficiency, highlighting the mechanistic continuum between these conditions. Finally, we systematically review emerging immunomodulatory interventions targeting the ovarian immune microenvironment, including strategies that restore Treg/Th17 balance, modulate macrophage polarization, and employ mesenchymal stem cells or platelet-rich plasma to remodel the immune niche. By integrating these mechanistic and therapeutic insights, this review aims to establish a coherent theoretical framework and future research directions for developing novel ovarian-protective interventions designed to improve reproductive outcomes and long-term health in aging women and those with POI.