Softening ovaries could extend fertility as women age, study suggests

Softening ageing ovaries could help women remain fertile for longer, early animal research suggests.

Fertility declines with age for several reasons, including poorer egg quality, fewer ovarian follicles and the gradual stiffening of ovarian tissue.

Existing fertility treatments, including hormone therapy and in vitro fertilisation, mainly address hormonal imbalances or help eggs mature or become fertilised.

Scientists are now examining whether changing the physical structure of the ovaries could provide another route for future fertility treatments.

Stuart A. Cook, of the Cardiovascular and Metabolic Disorders Programme at Duke-National University of Singapore Medical School, published an accompanying commentary on the research.

Researchers led by Shixuan Wang at Huazhong University of Science and Technology in Wuhan, China, collected healthy ovarian tissue from younger, middle-aged and older women.

They also examined samples from patients with polycystic ovary syndrome, known as PCOS, premature ovarian insufficiency, or POI, and endometriosis.

PCOS is a hormonal condition that can disrupt ovulation. POI occurs when the ovaries stop working normally before the age of 40, while endometriosis causes tissue similar to the womb lining to grow elsewhere in the body.

Tests of protein levels and gene activity found higher levels of the inflammatory protein interleukin-11, or IL-11, in ageing and diseased ovaries.

In laboratory experiments, the researchers exposed ovarian fibroblasts to IL-11. Fibroblasts are cells that produce connective tissue.

The protein caused the cells to produce excess collagen, a structural material that can build up during scarring and make tissue stiffer.

The researchers then genetically modified mice so they could not respond to IL-11. The animals developed less ovarian stiffening and maintained better ovarian function as they aged.

Similar results were seen in mouse models of PCOS and POI caused by chemotherapy.

In the final part of the experiment, older mice and rats were injected with a nanoparticle treatment containing small interfering RNA, or siRNA, designed to switch off IL-11.

The treatment made the animals’ ovaries less stiff and improved fertility.

Pregnancy rates among older mice rose from 25 per cent to 50 per cent, while average litter sizes also increased.

More rats treated with the therapy became pregnant and produced larger litters.

The approach remains highly speculative and will require considerably more research before its safety or effectiveness in women can be established.

However, the researchers said blocking the inflammatory pathway could eventually form the basis of new fertility treatments.

They said: “We propose that anti-IL-11 therapy represents a promising translational strategy for delaying ovarian ageing.”