Preprint: a map of the mouse ovary links tissue resistance to indentation with gene activity
Preprint: a map of the mouse ovary links tissue resistance to indentation with gene activity
On August 31, bioRxiv published a preprint, a preliminary version of a research paper in which investigators measured how fresh regions of mouse ovaries resisted indentation and compared these measurements with a map of gene activity from an adjacent section. Across 21 regions, they obtained 2 915 paired measurements. The map shows which cellular programs occur alongside different physical properties of the tissue.
The ovary continually remodels its connective tissue framework, the network of proteins between cells. Follicles grow within this framework, ovulation occurs, and the corpus luteum subsequently forms. The framework also changes with age. In 2020, ovaries from old mice resisted indentation about 2,5 times more strongly than ovaries from young mice. Collagenase, an enzyme that breaks down collagen, brought the elasticity of old tissue closer to that of young tissue. These measurements were taken at individual points on the surface of an intact ovary and revealed an overall age-related shift.
Within a single ovary, resistance can vary severalfold among different regions. The surrounding mechanical environment affects the growth of a follicle, the sac in which an egg matures. In 2025, researchers showed that theca cells, the outer layer of cells surrounding a follicle, assemble fibers of fibronectin, an extracellular matrix protein, around the follicle and compress it. Altering this pressure changed follicle growth. This study explains why an average for the whole organ conceals local biology.
The authors of the new preprint removed a thin, 100-micrometer section of fresh tissue from each ovary. The spherical tip of a nanoindenter, an instrument that presses into a surface and measures its resistance, moved across the section in a grid. An adjacent parallel surface lay beneath the section. The researchers froze this surface and used it to generate a spatial transcriptome, a point-by-point map of gene activity across the tissue. Images of the tissue and follicle boundaries allowed the two maps to be aligned within a shared coordinate system.
After quality control, 2 915 paired measurements remained from eight ovaries collected from young and 14-month-old mice. Each point on the mechanical map corresponded to an average of 92 regions on the gene activity map. Regions with greater resistance showed stronger activity of gene programs that cells activate in response to interferon signaling. More compliant regions showed stronger activity of gene programs associated with elastic fibers. The sets of associations differed between young and old animals. When the authors analyzed the anatomical compartments of the ovary separately, they identified 1 763 statistical associations between gene activity and resistance to indentation. An analysis averaged across the entire tissue identified 316.
A subsequent experiment could alter collagen, inflammation, or pressure, then use the two maps to determine which regions show concurrent changes in mechanical properties and gene activity.