The Effect of Maternal Age On the Ovarian Immune Milieu

Other than its protective role in defending against pathogens, the immune system has a crucial role in maintaining the body’s healthy physiology and homeostasis. In particular, immune cells which reside and infiltrate different sites in the female reproductive tract are part of the regulation of female fertility. These cells take part in maintaining the proper function of processes such as ovulation and pregnancy, as well as in regulating and setting the prognosis of ovarian cancer. However, from a certain age, both the fertility and the general immune function are found at a constant decline and our understanding of the role of maternal age on the interactions between the immune system and the female reproductive system is still lacking.

In this work, we characterized the immune milieu, at the single-cell level, in the ovaries of mice at different ages. We show an age-dependent change in the ovarian immune system which is independent of the cycle stage. Young mice showed macrophages (CD11b⁺ F4/80⁺) abundant ovarian immune system, whereas older ovaries showed a shift in their immune milieu toward a lymphocytes-rich (CD3⁺) immune system compared to their younger counterparts. These CD3⁺ lymphocytes contain TCRβ⁺ and TCRβ^- populations, both CD4^- CD8^- (Double negative). Our results suggest a significant organ-specific change in the immune milieu in the ovary throughout age.