How Changes in Ovarian Identity Post-Menopause Contribute to Inflammation

The traditional view held that after menopause, ovaries become dormant, but recent findings suggest these organs may contribute to postmenopausal inflammation.

Francesca Duncan from Northwestern University states, “We believed the ovaries had fulfilled their role after reproduction, yet our discoveries were quite unexpected.”

In a recent study published in March, Duncan and her team analyzed ovarian protein structures in women aged 50 to 75, expecting uniformity across samples. Conversely, they found that molecular signatures significantly changed over the decades, indicating a dynamic rather than static organ.

To explore these changes further, Duncan’s team investigated mouse ovaries, examining tissues and gene expression across various age groups: young (2 months), reproductive age (18 months), and post-reproductive (24 months).

Unlike humans, mice do not have menstrual cycles. Instead, their endometrial lining is reabsorbed. Also, while humans experience menopause, mouse fertility gradually declines with age, leading to irregular cycles. Duncan explains, “The decline in fertility and hormonal function mirrors what we see in aging mice.”

Expectedly, older ovaries showed a loss of egg-producing follicles and increased scarring. Moreover, genes responsible for reproduction and hormone production, specifically estradiol (a form of estrogen), were less active. However, genes linked to inflammation and immune activity were notably more active, with an increase in immune cells such as T cells and macrophages in aging ovaries.

Further investigation is needed to discern the implications of these findings for immune function and overall health. Duncan suggests that this might indicate a transformation in ovarian identity rather than an enhancement in immune capacity. “Ovaries seem to lose reproductive functions while gaining immune functions, which may not be beneficial,” she adds.

The phenomenon of chronic low-grade inflammation in aging tissues may involve the release of inflammatory molecules from the ovaries post-reproduction. Duncan remarks, “This shift in biological function could signal communication with other body systems, although its significance remains uncertain.”

Professor Diana Laird at the University of California, San Francisco posits that similar immune transformations may occur in humans, alluding to known reproductive similarities between species. “Both humans and mice cease cycling after their egg supply depletes, and experience similar changes like fibrosis and increased nerve distribution,” she notes.

While the rationale behind immune changes in older mice is still unclear, Laird suggests these adaptations might have offered an evolutionary advantage for surviving longer. However, such changes could also contribute to inflammation and autoimmune disorders under modern living conditions.

This study underscores the evolving role of ovaries post-menopause. While generally healthy, ovaries still release androgens, which help maintain bone density and libido. Laird asserts this research contributes to a growing understanding of how immune changes in ovaries may lead to increased inflammation, associated with conditions like rheumatoid arthritis in postmenopausal women. “This discovery emphasizes the need for comprehensive studies on the cellular and molecular aspects of post-reproductive ovaries,” she concludes.