Immunological Microenvironment Associated with the Ovaries and Its Modulation. During Aging

Abstract

Beyond its roles in gametogenesis and hormone secretion, the ovary encompasses a complex reproductive immunological microenvironment (RIM). This microenvironment is composed of diverse immune cells, including macrophages, T cells, dendritic cells, natural killer (NK) cells, and mast cells. These cells support oogenesis, steroidogenesis, and tissue remodelling. Macrophages stand out among these cells due to their functional plasticity and ability to integrate endocrine, immune, and neural signals. Thus, they participate in virtually all aspects of ovarian physiology. Aging disrupts this finely tuned environment through “inflammaging,” a chronic, low-grade systemic inflammatory state characterized by elevated proinflammatory mediators and tissue fibrosis. In the ovary inflammaging is associated with structural degeneration, fibro inflammation, and the accumulation of foam cells, which perpetuate inflammation and impair function. Additionally, emerging evidence highlights the role of extracellular vesicles and microRNAs (miRNAs) in regulating intercellular communication within the ovarian niche. This influences both follicular development and the decline in oocyte quality associated with aging. This mini-review discusses the interplay between immune modulation, inflammaging, and microRNA-mediated regulation in the ovarian microenvironment, emphasizing its implications for reproductive aging.