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Host transcriptomic responses of chicken embryos during Avian Pathogenic Escherichia coli infection reveal the significant role of the yolk sac in embryonic mortality

ABSTRACT: Colibacillosis caused by avian pathogenic Escherichia coli (APEC) is a major disease syndrome in poultry with the yolk sac infection recognized as a leading factor contributing to embryonic mortality. Yolk sac is the initial site of infection, however its contribution in embryonic mortality at molecular level has remained unexplored. To address this critical gap, we conducted RNA sequencing (RNA-seq) to analyze the comprehensive in vivo transcriptomic profiles of yolk sac and embryonic liver from APEC-infected embryos, comparing dead embryos with those that survived and mock-infected controls, to uncover key differences in host responses in multiple scenarios. Our results revealed that dead embryos displayed significant pro-inflammatory cytokine activity and cellular senescence, disrupted lipid and energy metabolism, and compromised antioxidative defenses, particularly in the yolk sac. In contrast, surviving embryos exhibited a regulated inflammatory response, enhanced mitochondrial activity, robust antioxidative responses and tissue repair mechanisms, which likely underpinned its resilience. Notably, yolk sac showed positive correlation (r = 0.531) with the embryonic liver, but demonstrated more severe inflammation and metabolic dysregulation, thereby highlighting its heightened vulnerability. Furthermore, reactive oxygen species (ROS) levels, the balance of the inflammatory response, and yolk sac integrity are crucial determinants of embryonic survival, with mitochondrial dysfunction serving as a key regulator of host immune and metabolic adaptation. The insights provide a deeper understanding of the previously overlooked role of yolk sac compared to liver during APEC infection, offering potential avenues for improving host resilience and mitigating economic losses in poultry.

ORGANISM(S): Gallus

PROVIDER: GSE300118 | GEO | 2025/07/21

REPOSITORIES: GEO

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Project description:The signaling cascades that direct the morphological differentiation of the vascular system during early embryogenesis are not well defined. To further understand the role of Notch signaling during endothelial differentiation, this study uses both an in vivo gain-of-function and in vivo loss-of-function approach. At embryonic day 9.5, embryos with activated Notch1 signaling in the endothelia display a variety of growth and cardiovascular defects, and die soon after E10.5. Most notably, the extra-embryonic vasculature of the yolk sac displays remodeling differentiation defects. In the wild-type yolk sac, the primary vascular network has begun to reorganize, forming the large primary vessels and the smaller capillaries. In the activated Notch1 embryos remodeling is defective; the vasculature have an enlarged surface with decreased inter-vessel space. Embryos with ablated Notch signaling also display growth and vascular defects at E9.5 similar to the activated Notch1 embryos, however they exhibit a lack of vascular remodeling in the yolk sac, retaining the simple vascular plexus seen at E8.5. These results indicate that Notch signaling plays a critical role in the remodeling of the vasculature in the early embryo, particularly in the extra embryonic region. A conditional transgenic system was used in this study to activate Notch signaling. The ubiquitous ROSA26Notch transgene with a Neo/stop cassette flanked by loxP sites, followed by the N1-ICD cDNA, was recombined with a Tie2-CRE mouse, resulting in the removal of the STOP cassette and the subsequent activation of the Notch1-intracellular domain. This allowed for the overexpression and expansion of Notch signaling in all endothelial cells. Male Tie2-Cre mice were mated with female ROSA26Notch mice and resulting embryos were dissected at embryonic day 9.5. To ablate Notch signaling, Tie2-Cre mice were used in a two generation cross to obtain Tie2-Cre; Rbpj flox/flox embryos. These embryos lack RBPJ binding activity in the endothelia. In both instances embryos were used for genotyping and the yolk sac were separated and used to isolate total RNA with an RNeasy mini kit. The RNA was analyzed with the Mouse Genome 430A Array from Affymetrix. Samples were performed in duplicate, and RNA from wild type yolk sac tissues was compared to activated Notch and RBPJ loss-of-function yolk sac tissues.

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Host transcriptomic responses of chicken embryos during Avian Pathogenic Escherichia coli infection reveal the significant role of the yolk sac in embryonic mortality

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