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Most people assume that the ovary is defunct once its reproductive role is complete – but that isn’t so. In fact, for decades after menopause, human ovaries experience inflammation and changes in tissue structure that could have implications for women’s health.
The ovary plays a fundamental role in female reproduction – but what happens post-menopause, once this job is done? A study from Northwestern University (IL, USA) and the Buck Institute (CA, USA) has begun to answer this question using mass spectrometry to conduct proteomic profiling of the ovaries. The findings raise important questions about women’s health, notably how postmenopausal ovaries may influence aging and chronic disease.
The ovary is one of the most rapidly aging organs in the human body, with functional decline gaining momentum in midlife and resulting in menopause around the age of 50. This has a significant impact on aging and healthspan; the onset of menopause has been linked to increased risk of ovarian cancer and chronic conditions, including cardiovascular disease, osteoporosis and neurodegeneration. Today, women can expect to live for decades after menopause; however, after this point, the ovary is poorly characterized – we know shockingly little about its biology and function, and it is often, incorrectly we now know, considered inactive.
“I would venture to say most people assume [the] ovaries are just sitting there doing nothing, similar to the appendix,” commented Francesca Duncan (Northwestern University), co-corresponding author of the recent work. “But that’s what makes this study very different.”
In a much-needed advance for the field, Duncan and colleagues mapped the proteomes of healthy human ovaries spanning the menopausal transition and the decades after. Using data-independent acquisition mass spectrometry, they identified 5812 protein groups in normal ovarian tissue from 28 postmenopausal women aged 50–75. Among these proteins, they observed progressive age-associated shifts, with 117 proteins significantly altered in ovaries aged 70 and over compared to those aged 50–59.
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The researchers then conducted various statistical tests, performing multivariate proteomic analysis to determine which proteins were driving the differences between age groups. There was a noticeable shift from proteins with RNA/gene-regulatory functions in younger ovaries to metabolic, trafficking and innate immune/complement pathways in older ovaries.
The team also combined differential abundance, multivariate modeling and covariate-adjusted linear modeling to define age-associated proteomic signatures in the postmenopausal ovary. Ovaries from younger women had more proteins involved in maintaining cell and tissue structure, whereas ovaries from older women had more proteins associated with extracellular matrix remodeling and inflammatory signaling, and fewer structural and keratin-associated proteins. These findings were used to develop a 26-protein consensus of postmenopausal ovarian aging called the Buck Postmenopausal Ovary Molecular Signature (BuckPOMS), which was validated by immunohistochemistry.
Finally, the scientists compared molecular features of postmenopausal ovarian aging with ovarian senescence and ovarian cancer-associated protein signatures, identifying some overlap that may suggest healthy ovarian aging and ovarian cancer share some biological processes.
Together, the results paint a more complex picture of the postmenopausal ovary than anyone expected. Evidently, the ovary continues to change even after its reproductive life ends, refuting its perception as an inert organ, although it remains to be seen what exactly this means for women’s health.
“Our data points to progressive aging features in which the ovary appears to lose its original identity and ends up doing something different,” Duncan added. “We do not yet know if there’s ever a point in a woman’s life when this organ is no longer beneficial and it’s actually harmful. These results really point to the need to ask this question.”
The post What happens to ovaries post-menopause? appeared first on BioTechniques.
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