Preprint: ovarian tissue becomes more resistant to deformation with age
Preprint: ovarian tissue becomes more resistant to deformation with age
A preprint published on September 8 reports measurements of this property in 132 participants attending reproductive medicine clinics. The authors compared ultrasound measurements with signs of tissue remodeling and outcomes of assisted reproductive technology (ART) cycles, in which hormones stimulate the ovaries to produce eggs for retrieval.
An egg matures inside a follicle, a small fluid-filled sac in the ovary. The follicle is surrounded by the stroma, which consists of cells and the extracellular matrix, the tissue’s protein framework. As collagen accumulates and the composition of this framework changes, the tissue becomes more resistant to deformation. This remodeling is called fibrosis.
Mouse experiments from 2020 provided the basis for the authors’ hypothesis: old ovaries were approximately 2,5 times more resistant to indentation, and collagenase, an enzyme that breaks down collagen, brought tissue elasticity closer to that of young ovaries. The authors of the new preprint investigated whether age-related remodeling could be detected in living patients.
They used shear-wave elastography, an ultrasound technique that tracks a wave through tissue to estimate its resistance to deformation. In 16 participants aged 33 or younger, the mean measurement was 13,3 kPa, compared with 18,8 kPa in 16 participants aged 37 or older. The unit kPa measures pressure. The maximum measurement and variability across measurements also increased with age. These associations persisted after accounting for AMH, a hormone used to assess follicle reserve, and body mass index. In a second cohort of 100 participants aged 24 to 45, the same three measures increased with age.
The authors examined whether the ultrasound measurements were consistent with changes in the tissue itself. Follicular fluid levels of C6M were lower in the older group than in the younger group. C6M is a fragment released when collagen VI breaks down. In ten participants, single-cell RNA analysis, which measures gene activity in individual cells, found the most pronounced age-related changes in stromal cells, involving genes associated with the extracellular matrix, tissue contraction, and inflammation. These findings are consistent with age-related remodeling of the stroma surrounding the follicles.
In the first cohort, a higher mean measurement was associated with fewer retrieved eggs and fewer mature eggs in models that accounted for age, AMH, and body mass index. Higher values were also associated with a smaller proportion of follicles maturing after hormonal stimulation. The authors propose testing whether this ultrasound measure could be useful in studies of interventions to modify fibrosis.