{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T16:14:59Z","timestamp":1785428099583,"version":"3.56.0"},"reference-count":96,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T00:00:00Z","timestamp":1779321600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007414","name":"Qassim University","doi-asserted-by":"publisher","award":["QU-APC-2026"],"award-info":[{"award-number":["QU-APC-2026"]}],"id":[{"id":"10.13039\/501100007414","id-type":"DOI","asserted-by":"publisher"}]},{"award":["QU-APC-2026"],"award-info":[{"award-number":["QU-APC-2026"]}],"id":[{"id":"https:\/\/ror.org\/01wsfe280","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Heat stress (HS) is among the most economically consequential environmental challenges to global dairy production, causing progressive declines in milk yield, compositional quality, and mammary cellular integrity. The temperature\u2013humidity index (THI) is the primary thermal load metric, with performance-impairment thresholds typically beginning at THI 68 in Holstein cattle, with severe impacts manifesting beyond THI 72; breed-specific thresholds for Jersey, Brown Swiss, and Simmental cows differ owing to their lower metabolic heat load and greater inherent thermotolerance. At the molecular level, HS activates heat shock protein networks\u2014notably HSPA1A, HSP90B1, and HSPH1\u2014through HSF1\/HSF4 transcriptional activation, while simultaneously suppressing casein genes (CSN1S1, CSN2, CSN3), lipogenic genes (FASN, SCD, CD36), amino acid transporters (SLC7A5, SLC38A2), and mTOR-AKT-STAT5 translational machinery, collectively impairing milk biosynthetic capacity. Pro-apoptotic signaling (BAX, CASP3 upregulation; BCL2 downregulation) and mitochondrial dysfunction further compromise mammary epithelial viability. Post-transcriptional regulation through miRNA, circRNA, and lncRNA competing endogenous RNA networks, alongside epitranscriptomic m6A modifications, adds further regulatory complexity. Genome-wide association studies have identified SNPs in HSP70A1A, HSPA4, TLR4, and PRLR as thermotolerance candidates compatible with sustained milk production. Nutritional supplementation with methionine, arginine, and taurine partially restores cellular synthetic capacity. Integrating multi-trait genomic selection with Bos indicus introgression, precision cooling, and targeted nutrition offers the most viable path toward climate-resilient, high-producing dairy cattle.<\/jats:p>","DOI":"10.3390\/biology15100813","type":"journal-article","created":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T05:33:54Z","timestamp":1779687234000},"page":"813","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Heat Stress Effects on Milk Production and the Genomic Architecture of Thermotolerance in Dairy Cattle"],"prefix":"10.3390","volume":"15","author":[{"given":"Qingshan","family":"Ma","sequence":"first","affiliation":[{"name":"College of Agriculture and Biology, Liaocheng University, Liaocheng 252000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3796-9590","authenticated-orcid":false,"given":"Mohamed","family":"Tharwat","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, College of Veterinary Medicine, Qassim University, P.O. Box 6622, Buraidah 51452, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7267-4301","authenticated-orcid":false,"given":"Fahad A.","family":"Alshanbari","sequence":"additional","affiliation":[{"name":"Department of Medical Biosciences, College of Veterinary Medicine, Qassim University, P.O. Box 6622, Buraidah 51452, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5890-2996","authenticated-orcid":false,"given":"Muhammad Zahoor","family":"Khan","sequence":"additional","affiliation":[{"name":"College of Agriculture and Biology, Liaocheng University, Liaocheng 252000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,21]]},"reference":[{"key":"ref_1","unstructured":"Food and Agriculture Organization of the United Nations (2024). 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