Self-organizing ovarian somatic organoids preserve cellular heterogeneity and reveal cellular contributions to ovarian aging

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 10, 2024

Abstract Ovarian somatic cells are essential for reproductive function, but no existing ex vivo models recapitulate the cellular heterogeneity or interactions within this compartment. We engineered a novel ovarian organoid model by culturing stroma-enriched fraction of mouse ovaries in scaffold-free agarose micromolds. organoids self-organized, maintained diverse cell populations, produced extracellular matrix, and secreted hormones. Organoids generated from reproductively old mice exhibited reduced aggregation growth compared to young counterparts, as well differences composition. Interestingly, matrix fibroblasts demonstrated upregulation pathways associated with actin cytoskeleton downregulation adhesion pathways, indicative increased stiffness which may impair aggregation. Cellular morphology, is regulated cytoskeleton, significantly changed age response depolymerization. Moreover, depolymerization rescued age-associated deficiency. Overall, have advanced fundamental knowledge contributions aging.

Language: Английский

Three-dimensional quantitative micro-elastography reveals alterations in spatial elasticity patterns of follicles and corpora lutea in murine ovaries during ageing

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 12, 2024

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

Language: Английский