Three-dimensional quantitative micro-elastography reveals alterations in spatial elasticity patterns in murine ovaries during ageing

Fibrosis and tissue stiffening are hallmarks of ovarian ageing, linked to a decrease in fertility. However, the lack of three-dimensional (3D) characterization of ovary elasticity limits our understanding of localized elasticity patterns and their connection to tissue composition. Here, we developed an integrated approach to link ovarian elasticity, volume, and cell-matrix composition using quantitative micro-elastography (QME), a label-free, non-invasive method to study 3D microscale elasticity in conjunction with immunofluorescence microscopy. QME reveals distinct spatial elasticity patterns in ovarian compartments, namely follicles and corpora lutea (CLs), and local elasticity alterations in different age cohorts. CL elasticity significantly increases, and follicle elasticity changes minimally with age. CLs show size-dependent elasticity changes, while follicles exhibit distinct spatial variations in elasticity correlated with the emergence of theca cell layers during follicle development. These findings have the potential to guide novel diagnostics and therapeutic targets to improve women's reproductive health and longevity.