Failed clearance of post-ovulatory debris drives ovarian fibroinflammation in mice

In a mouse study described in a new preprint, researchers investigated how post-ovulatory debris clearance contributes to ovarian fibroinflammation. Using a corpus luteum labeling system, laser capture microdissection, RNA sequencing, and histological analysis, the team examined reproductively old mice. They found that corpora lutea experienced dysregulated regression with age, leading to the accumulation of persistent corpora lutea alongside ovarian multinucleated giant cells. These persistent structures acted as focal hotspots for debris-associated and proinflammatory gene signatures enriched in lipids, extracellular matrix, and immune cells. Persistent structures retained luteal traits but transcriptionally resembled multinucleated giant cells. Extended culture of an ex vivo corpus luteum model also induced giant-cell features. In addition, treating isolated follicles or ovarian stromal organoids with factors from giant-cell-enriched explants drove compartment-specific fibroinflammatory responses.