Endometrial Signatures of Subfertility in Beef Heifers Reveal Dysregulation of MAPK Signaling and Ciliary Function.

BACKGROUND: Reproductive efficiency is a significant hurdle to the sustainability of the beef cattle industry. METHOD: This study employed transcriptomic profiling to investigate endometrial gene expression differences in heifers with divergent fertility outcomes. Caruncular endometrial samples from fertile (n = 7) and subfertile (n = 5) heifers were subjected to RNA-Seq analysis, yielding 894 differentially expressed genes (DEGs) (p ≤ 0.05 and |log2FC| ≥ 0.5). RESULTS: The MAPK (Mitogen-activated protein kinase) and Rap1 (Ras-associated protein 1) signaling pathways and immune response regulation were identified among the over-represented pathways underlying the DEGs. Transcriptional regulators, such as DUSP2, DUSP10, and MAPK13, were downregulated in subfertile heifers, suggesting disrupted signal transduction and immune function. Gene co-expression network analysis showed network rewiring and increased connectivity of genes related to cilium organization, motility, and microtubule-based processes in the subfertile group. Over-represented hub genes were enriched in the subfertile endometrium, including DNAH2, DNAI2, DNAAF4, CCDC65, and the transcription factor FOXJ1. Our results suggest that impaired ciliary function and disrupted MAPK and immune signaling could potentially contribute to subfertility. CONCLUSIONS: This study highlights novel molecular signatures in the uterine endometrium that may serve as predictive markers of fertility potential in beef heifers, providing a foundation for targeted strategies to improve reproductive performance in cattle.