The corpus luteum transcriptome is dysregulated in dairy cows with mastitis

Mastitis-induced inflammation in dairy cows can trigger premature luteolysis and subsequent pregnancy loss; however, the molecular mechanisms underlying these effects remain poorly understood. This study aimed to characterize changes in gene expression in the corpus luteum of cows with clinical or subclinical mastitis compared with healthy cows. Multiparous pregnant cows from a commercial pasture-based dairy herd were classified into three groups: subclinical mastitis (SCM; n = 6), clinical mastitis (CLM; n = 6), and healthy controls (CON; n = 5), based on California Mastitis Test scores and somatic cell counts. Corpus luteum biopsies were collected at pregnancy diagnosis, between 28 and 42 days post-insemination, using a transvaginal ultrasound-guided technique and subjected to RNA sequencing. Differential expression analysis identified 428 differentially expressed genes (DEG) between CLM and CON cows (263 upregulated and 165 downregulated), 186 between SCM and CON cows (76 upregulated and 110 downregulated), and 391 between CLM and SCM cows (236 upregulated and 155 downregulated; FDR < 0.05). Functional enrichment of DEG between CLM and CON showed dysregulation of pathways related to immune response, cortisol, GnRH, and oxytocin signaling. These transcriptional changes may reflect an adaptive luteoprotective response aimed at maintaining luteal function under systemic inflammatory stress. Overall, the results demonstrate that mastitis, particularly in its clinical form, markedly alters the luteal transcriptome during early pregnancy, potentially affecting corpus luteum function and contributing to an increased risk of pregnancy loss.