Comprehensive Profiling of ceRNA (circRNA-miRNA-mRNA) Networks in Hypothalamic-Pituitary-Mammary Gland Axis of Dairy Cows under Heat Stress.

Heat stress (HS) is directly correlated with mammary gland dysfunction and the hypothalamic-pituitary-mammary gland (HPM) axis is involved in regulating stress responses and lactation in dairy cows. Circular RNAs (circRNAs) play major roles in regulating transcription and post-transcription but their expression in the HPM axis of dairy cows under HS is still unclear. In the present study, we performed RNA sequencing to identify diferentially expressed (DE) circRNAs, DE microRNAs(miRNAs) and DEmRNAs, and performed bioinformatics analysis on those in HPM axis-related tissues of heat-stressed and normal cows. A total of 1680, 1112 and 521 DEcircRNAs, 120, 493 and 108 DEmiRNAs, 274, 6475 and 3134 DEmRNAs were identified in the hypothalamic, pituitary, and mammary gland tissues, respectively. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analyses indicated that the MAPK signaling pathway is potentially a key pathway. Competitive endogenous RNA (ceRNA) networks related to HS response and lactation regulation were established in three tissues. In conclusion, our results indicate that HS induces differential circRNA expression profiles in HPM axis-related tissues, and the predicted ceRNA network provides a molecular basis for regulating the stress response and lactation regulation in heat-stressed dairy cows.