Omics & gene networks

A systems genomics view of fescue toxicosis: Integrating immune, reproductive, microbial, and physiological responses in beef heifers

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Abstract

A systems genomics view of fescue toxicosis: Integrating immune, reproductive, microbial, and physiological responses in beef heifersCamila U. Braz, Joao Vitor G. Takashe, Breven Stark, Ahmed Sallam Fescue toxicosis imposes the greatest health-related cost in the U.S. grazing industry (more than $2 billion annually), largely due to its systemic impacts on growth, thermoregulation, and reproductive efficiency. Understanding organism-wide molecular responses is essential for identifying biomarkers of tolerance. This study aimed to characterize immune, reproductive, and microbial responses of beef heifers exposed to endophyte-infected tall fescue compared with control heifers. Twenty-four Simmental à— Angus heifers were assigned to endophyte-infected (E+; n=12) or endophyte-free (E−; n=12) tall fescue seeds for 49 days. Across the trial, E+ heifers exhibited classical toxicosis phenotypes, including reduced feed intake and body weight, as well as increased rectal temperature and respiration rate (P < 0.05). At the end of the trial, samples were collected for multi-omics profiling spanning different biological systems. Peripheral Blood Mononuclear Cells (PBMC) were analyzed by RNA-seq to assess immune responses (n=12); oocytes were aspirated to generate embryos (n=8) for transcriptomic evaluation of maternal molecular effects; and fecal samples (n=24) underwent full-length 16S rRNA sequencing to characterize microbial shifts. All sequencing data were quality-filtered; RNA-seq reads were aligned to the bovine reference genome (ARS-UCD2.0), and 16S rRNA sequences were classified using the SILVA reference database. In PBMCs, 64 genes were differentially expressed (FDR < 0.05), most of which were downregulated in E+ heifers. Functional enrichment revealed disruptions in inflammatory and immune processes, vascular regulation, cytokine production, and thermogenic pathways, consistent with impaired immune competence and altered heat-stress physiology. Embryos from E+ donors displayed 79 differentially expressed genes (all upregulated; FDR < 0.05). Many of these genes are usually activated only at later developmental stages, suggesting premature gene activation and developmental dysregulation likely resulting from altered maternal oocyte content. This pattern may contribute to reduced fertility under toxicosis. The microbiome of E+ heifers showed increased Desulfobacterota and decreased Actinobacteriota abundance (FDR < 0.05), taxa associated with acidosis risk and host immune regulation, respectively. The genus Bifidobacterium was significantly reduced (FDR < 0.05), consistent with previous reports linking its abundance to improved growth performance in cattle. Collectively, this integrated multi-omics analysis reveals coordinated immune suppression, early embryonic dysregulation, and microbial shifts in heifers exposed to fescue toxicosis. While we observed significant differential expression, we acknowledge that in bulk PBMC samples, these changes may reflect shifts in immune cell sub-population frequencies rather than, or in addition to, transcriptional regulation within specific cell types. These findings provide new insight into the biological architecture of fescue toxicosis and highlight candidate pathways and microbial signatures that may inform future genomic strategies for improving animal tolerance.

Keywords: 2026

How to Cite:

Braz, C., Takashe, J., Stark, B. & Sallam, A., (2026) “A systems genomics view of fescue toxicosis: Integrating immune, reproductive, microbial, and physiological responses in beef heifers”, World Congress on Genetics Applied to Livestock Production Digital Archive 2026(1): 2287245. doi: https://doi.org/10.31274/wcgalp.24245

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