Transcriptomic analysis reveals a crucial role of the yolk sac during Avian Pathogenic Escherichia coli infection in chicken embryos.

Colibacillosis caused by Avian Pathogenic Escherichia coli (APEC) is a major threat to poultry, and yolk sac infection is a leading cause of embryonic mortality. However, the molecular mechanisms and host responses during the infection have not yet been investigated. To address this, we performed RNA-seq to compare the in vivo transcriptomic profiles of yolk sac and embryonic liver from APEC-infected embryos in multiple scenarios, including dead, live, and mock-infected controls. In dead embryos, particularly in the yolk sac, marked pro-inflammatory cytokine activity, mitochondrial dysfunction, impaired fatty acid metabolism, and structural disruption were observed. In contrast, surviving embryos exhibited a regulated inflammatory response, enhanced oxidative phosphorylation and fatty acid oxidation, increased expression of antimicrobial peptides, strengthened antioxidant defenses, and tissue repair pathways. While yolk sac and liver responses were positively correlated, the yolk sac displayed greater inflammation and metabolic dysregulation, underscoring its vulnerability. These findings highlight the previously underappreciated role of the yolk sac in APEC pathogenesis and offer avenues to improve host resilience and mitigate losses in poultry production.