Aged Mouse Ovaries Show Loss of Reproductive Genes and Rise in Immune Activity

Ovaries in aged mice become infiltrated with immune cells and display heightened activity of inflammation-related genes, according to research led by Francesca Duncan at Northwestern University. The team examined ovarian tissue and gene expression in mice aged 2 months, 18 months and 24 months.

Older ovaries lost egg-producing follicles, developed more scarring and showed reduced activity of genes tied to reproduction and estradiol production.

Genes linked to inflammation and immune function instead increased in activity, and counts of T cells and macrophages rose with age. The study, which has not been peer reviewed, was published in the journal Molecular Human Reproduction. Duncan said the ovaries appear to lose reproductive characteristics and adopt an immune signature, though she does not view the shift as beneficial.

An earlier March analysis by the same group measured protein composition in ovaries from post-menopausal women aged 50 to 75. Molecular signatures varied substantially across the age range, indicating the organ continues to change rather than remain static.

Mice do not menstruate or undergo menopause but experience age-related loss of egg reserves and irregular cycles once oocyte numbers fall below a threshold.

Diana Laird at the University of California, San Francisco, said similar immune shifts are likely in humans because both species stop cycling at a critical oocyte threshold and share other age-related ovarian changes such as fibrosis. She noted that immune alterations in the ovaries may underlie increased inflammation linked to conditions such as rheumatoid arthritis after menopause.