Neural networks (white) and eggs (green) in a mouse ovary (left) and a fragment of a human ovary (right). Growing follicles containing eggs are depicted in magenta
Eliza Gaylord and Diana Laird, UCSF Laird Laboratory
A novel imaging technique has uncovered an unexplored ecosystem within the ovaries that could affect the aging process of human eggs. This breakthrough may pave the way for strategies to slow ovarian aging, maintain fertility, and enhance health after menopause.
Women are born with millions of immature eggs, with one maturing each month post-puberty. However, after the late 20s, fertility declines sharply, typically attributed to diminishing egg quantity and quality.
To gain insights into this decline, Eliza Gaylord and her team at the University of California, San Francisco, developed a 3D imaging method that visualizes eggs without the need for slicing the ovaries, a traditional technique.
These newly captured images revealed that eggs cluster in pockets, rather than being uniformly distributed, indicating that the ovarian environment may significantly influence egg aging and maturation.
By integrating this imaging with single-cell transcriptomics, which identifies cells by their gene expression, researchers examined over 100,000 cells from both mouse and human ovaries. Samples were taken from mice aged 2 to 12 months and four women aged 23, 30, 37, and 58.
Through this approach, the team identified 11 major cell types and uncovered some surprises. One unexpected finding was the presence of glial cells—typically associated with the brain—that nourish and repair nerve cells, alongside sympathetic nerve cells that manage the fight-or-flight response. In mice lacking sympathetic nerves, fewer eggs matured, suggesting these nerves may influence when eggs develop.
Moreover, the researchers observed that fibroblasts, crucial for structural support, decrease with age, potentially leading to inflammation and scarring in the ovaries of women in their 50s.
This research indicates that ovarian aging is influenced beyond just the eggs; it involves the surrounding ecosystem, as noted by Diana Laird, also affiliated with UCSF. Importantly, she highlights the similarities discovered between aging ovaries in mice and humans.
“These similarities provide a basis for using laboratory mice to model human ovarian aging,” states Laird. “With this roadmap, we can start to explore the mechanisms that dictate the pace of ovarian aging to devise treatments that might slow or reverse the process.”
One potential avenue is to adjust sympathetic nerve activity to slow egg loss, thereby extending the reproductive time frame and delaying menopause.
Whole eggs (green) and a subset of developing eggs (magenta) in the ovaries of 2-month-old (left) and 12-month-old (right) mice.
Eliza Gaylord and Diana Laird, UCSF Laird Laboratory
Theoretically, this approach not only preserves fertility but may also diminish the risk of common postmenopausal conditions, including heart disease. “While later menopause could increase the risk for some reproductive cancers, this pales in comparison to the 20-fold higher risk of death from cardiovascular disease post-menopause,” explaines Laird.
However, such interventions are likely still far in the future. Evelyn Telfer, a researcher at the University of Edinburgh—known for being the first to successfully culture human eggs outside the ovary—points out that the limited age range and samples from just four women restrict the applicability of the findings. “Though intriguing, this study’s results are too preliminary to support treatment strategies aimed at altering follicle utilization or slowing egg loss,” she notes.
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Source: www.newscientist.com
