Postmenopausal Ovaries May Shift From Reproduction to Immune Function, Study Finds

A study published in Molecular Human Reproduction by reproductive biologist Francesca Duncan of Northwestern University and colleagues suggests that ovaries may continue serving an important biological function after menopause. Research in mice indicates that, rather than becoming largely inactive once reproduction ends, aging ovaries may gradually shift toward supporting immune-related processes.

For many years, scientists believed the ovaries had little purpose after they stopped producing eggs. However, the new findings challenge that assumption, pointing to significant changes in ovarian activity later in life that could have broader implications for aging and long-term health.

Researchers Tracked Ovarian Changes Throughout Aging

To investigate how ovarian function changes over time, the researchers examined ovaries from mice aged 2, 18, and 24 months, representing different stages of the animals' reproductive lifespan. In mice, reproductive activity typically ends at around two years of age, making this a useful model for studying the life stage that roughly corresponds to menopause in humans.

One ovary from each animal was examined under a microscope to assess structural changes associated with aging. As anticipated, older mice had substantially fewer ovarian follicles, along with noticeable alterations in tissue organization and collagen structure, consistent with declining reproductive function.

The second ovary from each mouse underwent bulk RNA sequencing, a method that identifies which genes are actively producing proteins. While the activity of genes linked to reproduction declined with age, the researchers observed a significant increase in genes involved in immune function.

Older Ovaries Showed Signs of Increased Immune Activity

The analysis revealed a clear transition from a reproductive profile to one dominated by immune-related activity in post-reproductive ovaries. The researchers also found greater numbers of T cells, macrophages, and multinucleated giant cells within older ovarian tissue, all of which play important roles in immune and inflammatory responses.

According to Duncan and her colleagues, preliminary findings from human ovarian tissue suggest a similar pattern may occur after menopause. In an unpublished study involving ovarian samples from 28 women that has not yet undergone peer review, protein profiles differed according to age, indicating that postmenopausal ovaries continue to undergo molecular changes rather than becoming biologically inactive.

Findings Could Have Implications for Women's Health

Although mice do not experience the same rapid decline in estrogen that characterizes human menopause, they remain an important model because of their shared evolutionary biology with humans. The researchers say the findings raise the possibility that human ovaries also adopt a more immune-focused role after their reproductive function comes to an end.

The authors propose that this emerging immune activity could influence endocrine signaling as well as local biological processes throughout the body during aging. If confirmed, these changes could have important implications for understanding how the ovaries continue to affect health later in life, particularly for women who undergo surgical removal of their ovaries.

If postmenopausal ovaries contribute to regulating inflammation or immune responses, removing them through oophorectomy could affect the risk of age-related diseases in ways that extend beyond the well-established effects of hormone loss. Additional research in humans will be necessary to determine whether these changes influence cardiovascular health, brain function, bone health, or other aspects of healthy aging.

Researchers Say Many Questions Remain

The findings highlight how much scientists still have to learn about ovarian biology after menopause. As people are living longer and spending an increasing proportion of their lives beyond their reproductive years, researchers say understanding the changing role of the ovaries may become increasingly important for women's long-term health.