The first large-scale study across all major female reproductive organs has uncovered how aging processes impact each organ and tissue in unique ways. Published today in Nature Aging, the study has identified novel blood biomarkers that could help physicians anticipate health risks associated with menopause, such as pelvic floor prolapse.
“Until now, we tended to consider menopause mainly as the end of the ovary’s reproductive function,” says Marta Melé, PhD, leader of the transcriptomics and functional genomics group at the Barcelona Supercomputing Center (BSC) and director of the study. “However, our results show that it acts as a turning point that profoundly reorganizes other organs and tissues of the reproductive system, and allow us to identify the genes and molecular processes that could be behind these changes.”
Menopause is a complex biological process with significant implications for overall health, which is estimated to be actively affecting 6% of the world’s population at any given time. However, the cellular and molecular processes driving it across reproductive organs and tissues have historically remained understudied.
To map the complex biology of menopause, Melé’s team analyzed 1,112 tissue images and 659 RNA sequencing samples from 304 women between the ages of 20 and 70. This allowed the researchers to reconstruct aging trajectories of the uterus, ovary, vagina, cervix, breast, and Fallopian tubes. Using deep learning algorithms, they were able to identify key changes associated with aging in each organ, both at the molecular and tissue levels.
Results showed that not all organs age uniformly across the female reproductive system. For instance, the ovary and vagina were shown to age gradually in a process starting years before menopause. Meanwhile, the uterus undergoes a very abrupt transition during menopause.
Even within the same organ, different tissues were shown to age in distinct ways. In particular, the muscle tissue of the uterine wall and the vaginal epithelium were observed to be the most affected during menopause, undergoing sharp changes.
The study also analyzed blood plasma samples from 21,441 women, which led to the identification of molecular signals of aging that can be detected in the blood. These biomarkers could offer non-invasive monitoring of female reproductive organs during menopause and enable more accessible, less invasive follow-up tests for women at risk of complications associated with menopause, such as pelvic floor prolapse.
“We not only identified the molecular changes underlying the aging of these organs, but we also saw that they can be detected in blood, which opens the door to new clinical tools,” says Oleksandra Soldatkina, PhD, lead author of the study and researcher at BSC.
This study marks a step toward better understanding a key biological process that has historically been left behind, leading to better prevention, diagnosis and treatment of multiple diseases linked to menopause. The researchers highlighted that their findings “position menopause as a key inflection point in female aging and provide insights with tissue-specific focus to support healthier menopausal transitions and reduce age-related disease risk.”
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