Faulty debris clearance promotes ovarian fibroinflammation in mice

In reproductively old mice, impaired post-ovulatory debris clearance contributes to ovarian fibroinflammation, according to a preprint on bioRxiv. Each ovulation generates a corpus luteum, a transient structure that regresses if pregnancy does not occur. Using a corpus luteum-labeling system, researchers found that older mice experienced dysregulated regression, causing persistent corpora lutea to accumulate alongside ovarian multinucleated giant cells. Transcriptional and histological analyses revealed that these persistent structures formed focal hotspots enriched with lipids, extracellular matrix, and immune cells, sharing closer molecular similarities with giant cells than with normal corpora lutea. In an ex vivo model, prolonged culture caused corpora lutea to acquire giant cell-associated features. Additionally, culturing isolated ovarian follicles or stromal organoids with factors from giant-cell-enriched explants induced compartment-specific fibroinflammatory responses.