Scientists have identified a mechanism that causes ovarian tissue to stiffen with age, impairing reproductive function. Blocking the protein IL-11 helped improve ovarian performance in older mice and rats, and doubled the pregnancy rate in mice. The study was published in the journal Nature Aging.
“Blocking IL-11 signaling, both in a physiological model of ovarian aging and in various pathological models of ovarian dysfunction, holds significant therapeutic potential for enhancing ovarian function,” the paper states.
Researchers determined that one of the reasons for age-related decline in ovarian function is a change in tissue structure. Over time, more collagen accumulates in the organ, making the extracellular matrix denser and stiffer. This disrupts the normal development of follicles and reduces hormone production.
During the study, experts analyzed samples of human ovaries from different age groups, as well as tissues affected by various disorders, including polycystic ovary syndrome, endometriosis, and premature ovarian failure following chemotherapy. In all cases, scientists observed increased tissue stiffness and excess collagen.
The inflammatory protein IL-11 was found to play a key role in this process. Its levels rose with age in the ovaries of humans, mice, and rats. This mechanism activated connective tissue cells, which then produced more collagen, exacerbating fibrosis and compromising the organ’s condition.
Experiments showed that exposing mice to IL-11 led to increased tissue stiffness, reduced hormone levels, and diminished reproductive capacity. The animals had fewer healthy follicles and worse fertility indicators.
Scientists then tested the reverse approach by blocking the IL-11 signal. In mice with a disabled receptor for this protein, ovarian tissue remained softer, more follicles were preserved, and levels of reproductive-related hormones increased.
Additional trials were conducted on animals with chemotherapy-induced ovarian damage and a model of polycystic ovary syndrome. Suppressing IL-11 activity helped reduce collagen accumulation, lower tissue stiffness, and partially restore ovarian function.
In the final phase of the experiment, researchers used a drug based on small interfering RNA that reduced IL-11 production. After treatment, older mice and rats showed improvements in ovulation and fertility rates. In mice, the pregnancy rate rose from approximately 25% to 50%. Scientists note that these results have so far only been obtained in animal models, so further research is needed to assess the safety and effectiveness of the method in humans.
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