Organoid Reproduction

Self-Organizing Ovarian Somatic Organoids Preserve Cellular Heterogeneity and Reveal Cellular Contributions to Ovarian Aging

Dipali, S. S., A. Converse, M. Q. Gowett, et al. 2026. “ Self-Organizing Ovarian Somatic Organoids Preserve Cellular Heterogeneity and Reveal Cellular Contributions to Ovarian Aging.” Aging Cell 25, no. 1: e70333. https://doi.org/10.1111/acel.70333.
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ABSTRACT

Ovarian somatic cells are essential for reproductive function, but no existing ex vivo models recapitulate the cellular heterogene-ity or interactions within this compartment. We engineered an ovarian somatic organoid model by culturing a stroma- enrichedfraction of mouse ovaries in scaffold-free agarose micromolds. Self-organized ovarian somatic organoids maintained diverse cellpopulations, produced extracellular matrix, and secreted hormones. Organoids generated from reproductively old mice exhibitedreduced aggregation and growth compared to young counterparts, as well as differences in cellular composition. Interestingly,matrix fibroblasts from old mice demonstrated upregulation of pathways associated with the actin cytoskeleton and downregula-tion of cell adhesion pathways, indicative of increased cellular stiffness that may impair organoid aggregation. Cellular morphol-ogy, which is regulated by the cytoskeleton, significantly changed with age and in response to actin modulation. Moreover, actinmodulation altered organoid aggregation efficiency. Overall, ovarian somatic organoids have advanced knowledge of cellularcontributions to ovarian aging.

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