Aged mouse ovarian immune milieu shows a shift towards adaptive immunity and attenuated cell function

Abstract

The immune system plays a major role in maintaining many physiological processes in the reproductive system. However, a complete characterization of the immune milieu in the ovary, and particularly how it is affected by maternal aging, is still lacking. In this work, we utilize single-cell RNA sequencing and flow cytometry to construct a complete description of the murine ovarian immune system and its changes along with pre-estropause aging. We show that the ovarian immune cells composition undergoes an extensive shift with age towards adaptive immunity. We analyze the effect of aging on gene expression and chemokine and cytokine networks and show an overall decreased expression of inflammatory mediators together with an increased senescent cells recognition. Our results reveal the changes in the aging ovarian immune system of the fertile female as it copes with the inflammatory stimulations during repeated cycles and the increasing need for clearance of accumulating atretic follicles.