The time is ticking for prospective parents seeking to become pregnant: As women age, their fertility declines. A recent study on mice may shed light on this. The quantity of “stiff” tissue in the ovaries increases with age, and researchers have discovered that lowering this tissue—”softening” the ovaries, in other words—restored fertility in the animals. The same procedure may be effective in people.

Menopause marks the end of female fertility, but declines start around age 30. Scientists are still baffled as to why. Fibrosis, an aberrant development of stiff, sustaining material known as connective tissue, has lately been identified as a suspect. Fibrosis can harden our heart, lungs, liver, and ovaries as we age, as Duncan and her associates discovered in 2016.

First, the researchers administered a fibrosis-reduction medication to 15-month-old mice, which are about equal to people in their early 50s. The team describes their findings in today’s issue of Science Advances. These rodents are typically too elderly to breed, but the medicine allowed more than half of them to ovulate. The development of apparently healthy embryos in a test dish when the researchers fertilized the resultant eggs suggests the eggs were healthy.

The mice were past the age of reproduction, unlike the majority of people at reproductive clinics. The medicine was therefore also tested on 12-month-old mice, which are the equivalent of 35-year-old humans. Once more, the drug stimulated the animals’ reproductive processes, nearly tripling the amount of eggs they released. In vitro fertilization revealed that the eggs were healthy because it resulted in the development of embryos. Even juvenile animals were unaffected by the treatment, though.

Despite these accomplishments,the researchers weren’t certain whether lessened fibrosis was what caused the increased fertility,because fibrosis includes the buildup of hard collagen strands.However, when the researchers examined the ovaries of the animals under a microscope, they discovered that both groups of treated mice had far less fibrosis than the untreated mice.

Ovarian fibrosis may be exacerbated by damaged mitochondria, the organelles that provide energy to cells. These structures start to malfunction as mice and people age, producing fewer of the energy-rich chemicals that cells require and more harmful metabolic byproducts.

Researchers administered a separate medication, BGP-15, which tunes up the organelles, to 14-month-old mice in order to investigate the role of mitochondria in infertility. The animals ovulated more than twice as many eggs and displayed less fibrosis in their ovaries than untreated mice of the same age.

The scientists also examined two other chemicals that support mitochondria: MitoQ, a popular anti-aging supplement, and metformin, an anti-diabetes medication occasionally recommended for infertility. Both compounds reduced ovarian fibrosis in aged animals but had no ovulation-inducing effects.

Human obesity reduces fertility, however it is not known if ovarian fibrosis contributes to this loss. The ovaries of young, fat mice had a high prevalence of fibrosis, the researchers found. Additionally, they discovered that in these animals, BGP-15, metformin, and MitoQ reduced the fiber buildup and promoted ovulation.

Although it’s unclear how fibrosis affects fertility, researchers speculate that it might cause ovarian tissue to become hard. A follicle, also known as a cradle, in which an egg develops swells to around 1 million times its initial size before bursting to deliver the egg. Connective tissue accumulation may confine follicles, preventing them from expanding and obstructing the generation of eggs. According to the study’s findings, BGP-15 stimulates mice to create an enzyme that breaks down the collagen fibers in connective tissue, perhaps releasing the follicles.

Clinical trials to test BGP-15 or other fibrosis-reversing agents may be able to be started by researchers. It can be difficult to tell who has acquired fibrosis because the ovaries are hidden deep inside the belly; fibrosis is typically discovered when the ovaries are surgically removed. A non-intrusive approach has to be found, the experts suggest.