For years we have told them like this: the eggs are finished, the work is finished. Convenient, linear and perhaps wrong. The ovaries after menopause continue to change and could take on a role linked to the immune system, accumulating inflammatory cells and producing signals capable of reaching other tissues.
This is what a study published on suggests Molecular Human Reproductionwhich describes the transition from a reproductive organ to a tissue with a marked immune identity. A hypothesis yet to be explored further, but destined to change the way we look at the ovaries during the many years following the end of the fertile age.
The ovaries continue to change
The tests compared the ovaries at three different stages of life: full reproductive age, progressive exhaustion of fertility and the period following the cessation of ovulation. Some of the tissues were observed under the microscope. The other was analyzed through RNA sequencing, a technique that allows us to identify the most active genes within an organ.
With age, follicles, the small structures that contain oocytes, decreased, while collagen increased. The tissue became more fibrous and progressively lost markers linked to gamete production, meiosis and hormone synthesis.
The change continued even after the cessation of ovulation. At that point the number of follicles and the level of fibrosis now appeared stable, while the genetic activity continued to change. The end of fertility, therefore, left an ovary still biologically active.
From reproductive organ to immune tissue
The genes linked to reproductive function decreased. On the other hand, those involved in immune responses, the production of cytokines and the activation of leukocytes increased. Inside the ovaries, T lymphocytes, macrophages and multinucleated giant cells increased. The latter often appear in tissues affected by chronic inflammation, accumulation of cellular debris and remodeling processes.
The researchers speak of an organ with an identity “similar to the immune one”. The formula describes the new composition of the tissue and its molecular activity; the precise function still remains to be clarified.
Immune cells could be called upon by the aging ovary. Even the ovarian cells already present could lose some original characteristics and acquire new ones. To distinguish the two processes, analyzes of single cells and studies capable of following their evolution over time will be needed.
Inflammatory signals to the rest of the body
The tests also identified a variation in factors potentially secreted by the ovaries. With the exhaustion of the reproductive function, the molecules produced by the oocytes decreased and immunoglobulins and components of the complement system, one of the main tools of the immune response, increased. These substances could act on surrounding tissues or enter the blood circulation and reach other organs. This is where research meetsinflammagingthe chronic low-intensity inflammation associated with aging.
In women, age is often accompanied by increased activity of certain inflammatory pathways, higher levels of cytokines, and changes in the immune response. The ovaries could contribute to this environment through signals that have so far remained out of the picture. The actual presence of these proteins in the blood has yet to be verified. It will also be necessary to understand whether they really manage to modify the behavior of distant tissues.
The first traces in human tissues
A first indication comes from a second study still awaiting peer review. The researchers analyzed healthy ovarian samples from 28 women between 50 and 75 years old, divided into three age groups. 5,812 protein groups were measured. In the comparison between women aged 50-59 and those at least 70 years old, 117 were significantly different.
In older ovaries, signatures associated with innate immunity, the complement system, inflammation and remodeling of the extracellular matrix, the network that supports cells, increased. Some factors secreted in response to tissue damage also increased. The sample remains small and covers a limited demographic range. The result, however, follows the same direction: the ovaries continue to remodel themselves for decades after menopause.
A new piece of women’s health
The ovaries already maintain a hormonal function after menopause. They continue to produce testosterone, other androgens, and smaller amounts of estrogen. This residual activity has favored a more prudent approach to oophorectomy, the surgical operation that involves their removal, especially in the presence of benign conditions.
The possible immune function adds another element to a choice that depends on the age, oncological risk, family history and conditions of the individual patient. The clinical consequences of these findings still remain open. In the future, better understanding the inflammatory environment of the ovaries could lead to therapies aimed at women’s health after menopause, targeting inflammation rather than trying to restore fertility. Fertility stops. The ovaries continue to change.
