Heat Tolerance-Associated circRNA3685 Regulates Apoptosis and Autophagy in Bovine Mammary Epithelial Cells via Sponging bta-miR-138

Heat stress negatively affects dairy cow production, and health, leading to significant losses. Identifying mechanisms associated with heat tolerance is crucial for developing breeding strategies. Circular RNAs (circRNAs), a type of noncoding RNA, regulate cell functions like autophagy, apoptosis and proliferation. In this study, dairy cows were classified into heat stress tolerant (HST, n = 15) and heat stress sensitive (HSS, n = 15) groups based on respiratory and drooling score during the heat stress. A significant difference in milk production decline was observed, with the HST group showing less decline, indicating better heat tolerance. Blood transcriptomics analysis identified 166 differentially expressed circRNAs with circRNA3685 being highlighted as a key candidate linked to heat tolerance. Overexpression of circRNA3685 in bovine mammary (MAC-T) cells inhibited autophagy and apoptosis. The circRNA3685 was found to interact with bta-miR-138, targeting HIF1A. These findings provide insights into circRNAs' role in heat stress adaptation in dairy cows.