Are the ovaries responsible for declining fertility?

Between the ages of 25 and 40, the chances of conceiving naturally decrease drastically. While a woman has about a 25% chance of conceiving each month at age 25, this figure drops to less than 5% at age 40. Until now, the exact causes of menopause have not been pinpointed. Genetics are known to play a role, as do certain behaviors such as smoking, and weight. But a new study may have found the key to declining fertility... and it may lie in the ovary. Cellular changes in this organ have a major influence on ovarian maturation, according to a study published in the journal Science.

In men, fertility peaks between the ages of 20 and 40 before slowly declining. But in most cases, it is maintained until the end of life. Women, on the other hand, experience menopause, the permanent cessation of fertility. Its most visible symptom is the cessation of menstruation for at least a year. It generally occurs between the ages of 48 and 52, either when the woman no longer has enough follicles to allow fertilization, or when the remaining ones have degenerated.

Eggs stored in clusters

To try to better understand how fertility evolves over time, the team from the University of California (UCLA), which is behind this new work, wanted to observe what was happening in the ovaries using 3D imaging. “ We were surprised to see that inside, the eggs are not distributed all over the place, as we usually imagine." explains Professor Diana Laird, who teaches obstetrics at UCLA and who authored this work. Our results show that the environment around the eggs – the nerve cells and tissues – also changes over time. In fact, the eggs are grouped in clusters in places in the ovary where they feel comfortable.. »

A human ovary in which the egg cells (in green), grouped in clusters, and the sympathetic nerves (in white) are visible. Credits: LAIRD / SCIENCE

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11 different cell types in the ovaries

The analyses, conducted on mice and humans, identified 11 types of cells in the ovaries, including some completely unexpected ones: glial cells, a type of nerve cell generally found in the brain, as well as networks of sympathetic nerves, which are responsible for the response. fight or flight"These play a key role in regulating egg growth in the ovary. When we genetically prevented the survival of sympathetic nerves in mice, we observed more resting eggs and fewer developing eggs, suggesting that the nerves participate in the awakening of eggs in their follicles and support their growth and maturation. In both human and mouse ovaries, we found that sympathetic nerve networks become denser at older reproductive ages. »

For the moment, the exact role of sympathetic nerves and glial cells in follicular maturation has not yet been established. A three-way interaction between nerves, blood vessels, and growing follicles, which the team is currently seeking to better understand through new work. Another type of cell surprised the researchers here: fibroblasts, which are better known for appearing in other organs such as the lungs or liver with age. But from the age of 50, the team also found them in the ovary, causing inflammation and scar tissue.

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With these results, the team hopes to find ways to preserve fertility. By modulating sympathetic signaling (that is to say by blocking the action of the sympathetic nerves, editor's note), or by manipulating signals from blood vessels, it may be possible to slow the loss of ovaries, extend the reproductive window and potentially delay the onset of menopause.", hopes Professor Laird. " And women live a third of their lives after menopause" she recalls.

A period during which cardiovascular risk increases. Better identifying vascular changes in the ovary could help understand their vascular health more broadly" Building on these initial advances, the team has already launched new work. It hopes to succeed in inducing the desired effect using different molecules.