Three-dimensional quantitative micro-elastography reveals alterations in spatial elasticity patterns of follicles and corpora lutea 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 the tissue composition. Here, we developed an integrated approach to link ovarian tissue elasticity, volume, and cell-matrix composition using quantitative micro-elastography (QME), a label-free, non-invasive approach to study the 3D microscale elasticity in conjunction with immunofluorescence microscopy. QME revealed distinct spatial elasticity patterns in ovarian compartments, namely follicles and corpora lutea (CLs), and local elasticity alterations in different age cohorts. For example, CL elasticity significantly increased during ovarian ageing while follicle elasticity changed minimally. CLs showed size-dependent elasticity changes, while follicles exhibited distinct spatial variations in elasticity correlated with the emergence of theca cell layers during follicle development. These findings have the potential to guide the development of novel diagnostic tools and identify therapeutic targets, improving women’s reproductive health and longevity.