{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T03:06:11Z","timestamp":1784948771333,"version":"3.55.0"},"reference-count":51,"publisher":"Bioscientifica","issue":"1","license":[{"start":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T00:00:00Z","timestamp":1781481600000},"content-version":"vor","delay-in-days":165,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["journals.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,1,1]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>With rising global temperatures, it is imperative to determine the impact of heat stress on the physiology of food-producing animals. Dairy cows are susceptible to uterine diseases that reduce fertility. Immune function is important in the development and progression of disease; however, the effect of heat shock on the innate immune capacity of endometrial epithelial cells remains underexplored. Here, we investigated how heat shock alters the innate immune response and mitochondrial respiration of bovine endometrial epithelial cells. Primary endometrial epithelial cells were collected from postpartum cows and cultured in the presence of lipopolysaccharide under thermoneutral (38.5\u00b0C) or heat shock (40.0\u00b0C) conditions. Time-course and sequential heat shock experiments were conducted to assess gene expression dynamics of HSPA1A, TLR4, CXCL8, IL6, and IL1B. Cell viability was evaluated by MTT assay, and mitochondrial respiration was analyzed using high-resolution respirometry. Heat shock did not affect cell viability or overall mitochondrial respiration but reduced proton leak-related oxygen consumption. Acute heat shock induced HSPA1A expression but suppressed LPS-stimulated CXCL8 and IL6 expression. Expression of TLR4 increased when cells were recovering from heat shock or following sequential heat shock. Sequential heat shock did not affect the expression of pro-inflammatory mediators compared to a single heat shock event. In conclusion, acute heat shock of bovine endometrial epithelial cells reduced the innate immune response to LPS without impacting cell viability or mitochondrial function. Altered endometrial immune function may contribute to the increased incidence of uterine diseases in cows under heat stress conditions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Lay summary<\/jats:title>\n                    <jats:p>As global temperatures continue to rise, food-producing animals face increasing challenges to their fertility and productivity. Uterine disease in dairy cows reduces fertility and impacts milk production. Heat stress is known to disrupt immune function, but less is understood about how elevated temperatures affect the cells that line the uterus that respond to invading pathogens. We examined how acute heat exposure affects the immune response of uterine cells to respond to pathogens and found that heat shock reduces their ability to produce key immune molecules needed to fight bacteria. This suggests that heat stress directly weakens the natural defenses of the uterus and helps us understand why cows are vulnerable to reproductive diseases during hot weather. Understanding these effects can guide better management strategies to protect animal health in a warming climate.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1530\/raf-25-0213","type":"journal-article","created":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T12:15:13Z","timestamp":1770725713000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-13","source":"Crossref","is-referenced-by-count":1,"title":["Heat shock suppresses the innate immune response of bovine endometrial epithelial cells"],"prefix":"10.1530","volume":"7","author":[{"given":"Arslan","family":"Tariq","sequence":"first","affiliation":[{"name":"1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masroor","family":"Sagheer","sequence":"additional","affiliation":[{"name":"1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zachary K","family":"Seekford","sequence":"additional","affiliation":[{"name":"1"},{"name":"2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junxiao","family":"Ren","sequence":"additional","affiliation":[{"name":"1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Yue","sequence":"additional","affiliation":[{"name":"1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5438-2137","authenticated-orcid":true,"given":"John J","family":"Bromfield","sequence":"additional","affiliation":[{"name":"1"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","published-online":{"date-parts":[[2026,2,10]]},"reference":[{"key":"2026070714090036500_bib1","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1146\/annurev-animal-031412-103644","article-title":"Effects of heat stress on postabsorptive metabolism and energetics","volume":"1","author":"Baumgard","year":"2013","journal-title":"Annu Rev Anim Biosci"},{"key":"2026070714090036500_bib2","doi-asserted-by":"crossref","first-page":"471","DOI":"10.3168\/jds.2013-6611","article-title":"The effects of heat stress in Italian Holstein dairy cattle","volume":"97","author":"Bernabucci","year":"2014","journal-title":"J Dairy Sci"},{"key":"2026070714090036500_bib3","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1038\/s41577-019-0159-y","article-title":"Getting enough energy for immunity","volume":"19","author":"Bird","year":"2019","journal-title":"Nat Rev Immunol"},{"key":"2026070714090036500_bib4","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1002\/cyto.a.24777","article-title":"Impact of enzymatic digestion on single cell suspension yield from peripheral human lung tissue","volume":"103","author":"Bondonese","year":"2023","journal-title":"Cytometry A"},{"key":"2026070714090036500_bib5","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1042\/BJ20110162","article-title":"Assessing mitochondrial dysfunction in cells","volume":"435","author":"Brand","year":"2011","journal-title":"Biochem J"},{"key":"2026070714090036500_bib6","doi-asserted-by":"crossref","first-page":"2021","DOI":"10.2527\/jas.2014-8496","article-title":"Physiology and endocrinology symposium: uterine infection: linking infection and innate immunity with infertility in the high-producing dairy cow","volume":"93","author":"Bromfield","year":"2015","journal-title":"J Anim Sci"},{"key":"2026070714090036500_bib7","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1373\/clinchem.2008.112797","article-title":"The MIQE guidelines: minimum information for publication of quantitative real-time PCR experiments","volume":"55","author":"Bustin","year":"2009","journal-title":"Clin Chem"},{"key":"2026070714090036500_bib8","doi-asserted-by":"crossref","first-page":"3212","DOI":"10.4049\/jimmunol.162.6.3212","article-title":"Human 60 kDa heat shock protein: a danger signal to the innate immune system","volume":"162","author":"Chen","year":"1999","journal-title":"J Immunol"},{"key":"2026070714090036500_bib9","doi-asserted-by":"crossref","first-page":"3145","DOI":"10.1016\/j.febslet.2006.04.066","article-title":"Hsp70 inhibits lipopolysaccharide-induced NF-kappaB activation by interacting with TRAF6 and inhibiting its ubiquitination","volume":"580","author":"Chen","year":"2006","journal-title":"FEBS Lett"},{"key":"2026070714090036500_bib10","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/j.molcel.2014.03.030","article-title":"Stress, inflammation, and defense of homeostasis","volume":"54","author":"Chovatiya","year":"2014","journal-title":"Mol Cell"},{"key":"2026070714090036500_bib11","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1095\/biolreprod.111.092718","article-title":"Toll-like receptor 4 and MYD88-dependent signaling mechanisms of the innate immune system are essential for the response to lipopolysaccharide by epithelial and stromal cells of the bovine endometrium","volume":"86","author":"Cronin","year":"2012","journal-title":"Biol Reprod"},{"key":"2026070714090036500_bib12","doi-asserted-by":"crossref","first-page":"116","DOI":"10.3389\/fvets.2020.00116","article-title":"Heat stress impacts immune status in cows across the life cycle","volume":"7","author":"Dahl","year":"2020","journal-title":"Front Vet Sci"},{"key":"2026070714090036500_bib13","doi-asserted-by":"crossref","first-page":"260","DOI":"10.14202\/vetworld.2016.260-268","article-title":"Impact of heat stress on health and performance of dairy animals: a review","volume":"9","author":"Das","year":"2016","journal-title":"Vet World"},{"key":"2026070714090036500_bib14","first-page":"p 240","article-title":"Toll-like receptors 2 (TLR2) and 4 (TLR4) of porcine blood leukocytes during heat-stress","author":"Eicher","year":"2004","journal-title":"Veterinary Immunology International Symposium"},{"key":"2026070714090036500_bib15","doi-asserted-by":"crossref","first-page":"761","DOI":"10.2460\/javma.1988.192.06.761","article-title":"Incidence and types of clinical mastitis in dairy herds with high and low somatic cell counts","volume":"192","author":"Erskine","year":"1988","journal-title":"J Am Vet Med Assoc"},{"key":"2026070714090036500_bib16","doi-asserted-by":"crossref","first-page":"37","DOI":"10.3390\/ani7050037","article-title":"Practices for alleviating heat stress of dairy cows in humid continental climates: a literature review","volume":"7","author":"Fournel","year":"2017","journal-title":"Animals"},{"key":"2026070714090036500_bib17","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1016\/j.cell.2019.01.050","article-title":"Energetic trade-offs and hypometabolic states promote disease tolerance","volume":"177","author":"Ganeshan","year":"2019","journal-title":"Cell"},{"key":"2026070714090036500_bib18","doi-asserted-by":"crossref","first-page":"6660","DOI":"10.3168\/jds.2018-16011","article-title":"Influence of on-farm measurements for heat stress indicators on dairy cow productivity, female fertility, and health","volume":"102","author":"Gernand","year":"2019","journal-title":"J Dairy Sci"},{"key":"2026070714090036500_bib19","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1186\/1477-7827-6-44","article-title":"Phospholipase A2 regulation of bovine endometrial (BEND) cell prostaglandin production","volume":"6","author":"Godkin","year":"2008","journal-title":"Reprod Biol Endocrinol"},{"key":"2026070714090036500_bib20","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1038\/sj.bjp.0704889","article-title":"Functional characterization of serum- and growth factor-induced phenotypic changes in intact bovine tracheal smooth muscle","volume":"137","author":"Gosens","year":"2002","journal-title":"Br J Pharmacol"},{"key":"2026070714090036500_bib21","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1379\/1466-1268(1997)002<0132:MSPHIW>2.3.CO;2","article-title":"Major stress protein Hsp70 interacts with NF-kB regulatory complex in human T-lymphoma cells","volume":"2","author":"Guzhova","year":"1997","journal-title":"Cell Stress Chaperones"},{"key":"2026070714090036500_bib22","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.11576","article-title":"Molecular mechanism of thermosensory function of human heat shock transcription factor Hsf1","volume":"5","author":"Hentze","year":"2016","journal-title":"Elife"},{"key":"2026070714090036500_bib23","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1530\/REP-07-0229","article-title":"Ovarian follicular cells have innate immune capabilities that modulate their endocrine function","volume":"134","author":"Herath","year":"2007","journal-title":"Reproduction"},{"key":"2026070714090036500_bib24","doi-asserted-by":"crossref","first-page":"1547","DOI":"10.3168\/jds.S0022-0302(89)79266-3","article-title":"Field survey of clinical mastitis in low somatic cell count herds","volume":"72","author":"Hogan","year":"1989","journal-title":"J Dairy Sci"},{"key":"2026070714090036500_bib25","volume-title":"Climate Change 2023: Synthesis Report. Contribution of Working Groups I, II and III to The Sixth Assessment Report of The Intergovernmental Panel On Climate Change","author":"IPCC","year":"2023"},{"key":"2026070714090036500_bib26","doi-asserted-by":"crossref","first-page":"1462","DOI":"10.1017\/S1751731114001268","article-title":"Heat stress upregulation of toll-like receptors 2\/4 and acute inflammatory cytokines in peripheral blood mononuclear cell (PBMC) of bama miniature pigs: an in vivo and in vitro study","volume":"8","author":"Ju","year":"2014","journal-title":"Animal"},{"key":"2026070714090036500_bib27","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1262\/jrd.2013-067","article-title":"Low incidence of an altered endometrial epidermal growth factor (EGF) profile in repeat breeder Holstein heifers and differential effect of parity on the EGF profile between fertile Holstein (dairy) and Japanese black (beef) cattle","volume":"59","author":"Katagiri","year":"2013","journal-title":"J Reprod Dev"},{"key":"2026070714090036500_bib28","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1093\/af\/vfad052","article-title":"Physiological impact of amino acids during heat stress in ruminants","volume":"13","author":"Loor","year":"2023","journal-title":"Anim Front"},{"key":"2026070714090036500_bib51","doi-asserted-by":"crossref","first-page":"12689","DOI":"10.3168\/jds.2025-26980","article-title":"Mild heat stress effects on hepatic and mammary mitochondria of lactating dairy cattle","volume":"108","author":"Marquez Acevedo","year":"2025","journal-title":"J Dairy Sci"},{"key":"2026070714090036500_bib29","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1016\/j.neuroscience.2008.07.067","article-title":"Toll-like receptor signaling in endogenous neuroprotection and stroke","volume":"158","author":"Marsh","year":"2009","journal-title":"Neuroscience"},{"key":"2026070714090036500_bib30","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1126\/science.1071059","article-title":"The danger model: a renewed sense of self","volume":"296","author":"Matzinger","year":"2002","journal-title":"Science"},{"key":"2026070714090036500_bib31","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1038\/nature07201","article-title":"Origin and physiological roles of inflammation","volume":"454","author":"Medzhitov","year":"2008","journal-title":"Nature"},{"key":"2026070714090036500_bib32","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1016\/j.cell.2016.08.064","article-title":"Succinate dehydrogenase supports metabolic repurposing of mitochondria to drive inflammatory macrophages","volume":"167","author":"Mills","year":"2016","journal-title":"Cell"},{"key":"2026070714090036500_bib33","doi-asserted-by":"crossref","DOI":"10.1016\/j.jtherbio.2023.103564","article-title":"Inflammatory responses of bovine endometrial epithelial cells are increased under in vitro heat stress conditions","volume":"114","author":"Molinari","year":"2023","journal-title":"J Therm Biol"},{"key":"2026070714090036500_bib34","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.theriogenology.2022.08.001","article-title":"Effect of calving season on metritis incidence and bacterial content of the vagina in dairy cows","volume":"191","author":"Molinari","year":"2022","journal-title":"Theriogenology"},{"key":"2026070714090036500_bib35","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1038\/nature11862","article-title":"Metabolism of inflammation limited by AMPK and pseudo-starvation","volume":"493","author":"O\u2019Neill","year":"2013","journal-title":"Nature"},{"key":"2026070714090036500_bib36","doi-asserted-by":"crossref","first-page":"2936","DOI":"10.1210\/endo.143.8.8969","article-title":"Expression of microsomal prostaglandin E synthase in bovine endometrium: coexpression with cyclooxygenase type 2 and regulation by interferon-tau","volume":"143","author":"Parent","year":"2002","journal-title":"Endocrinology"},{"key":"2026070714090036500_bib37","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/S0005-2728(00)00246-2","article-title":"Mitochondrial proton leak: a role for uncoupling proteins 2 and 3?","volume":"1504","author":"Porter","year":"2001","journal-title":"Biochim Biophys Acta"},{"key":"2026070714090036500_bib38","doi-asserted-by":"crossref","first-page":"217","DOI":"10.3168\/jdsc.2021-0189","article-title":"Culture of endometrial epithelial cells collected by a cytological brush in vivo","volume":"3","author":"Rocha","year":"2022","journal-title":"JDS Commun"},{"key":"2026070714090036500_bib39","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1262\/jrd.2018-051","article-title":"Heat stress affects prostaglandin synthesis in bovine endometrial cells","volume":"64","author":"Sakai","year":"2018","journal-title":"J Reprod Dev"},{"key":"2026070714090036500_bib40","doi-asserted-by":"crossref","DOI":"10.14814\/phy2.14640","article-title":"Alteration of chemokine production in bovine endometrial epithelial and stromal cells under heat stress conditions","volume":"8","author":"Sakai","year":"2020","journal-title":"Physiol Rep"},{"key":"2026070714090036500_bib41","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.1002\/jcp.30604","article-title":"Hyperthermia alters interleukin-6 production in response to lipopolysaccharide via endoplasmic reticulum stress in bovine endometrial cells","volume":"237","author":"Sakai","year":"2022","journal-title":"J Cell Physiol"},{"key":"2026070714090036500_bib42","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1146\/annurev-animal-020518-115227","article-title":"Tolerance and innate immunity shape the development of postpartum uterine disease and the impact of endometritis in dairy cattle","volume":"7","author":"Sheldon","year":"2019","journal-title":"Annu Rev Anim Biosci"},{"key":"2026070714090036500_bib50","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.femsyr.2004.04.008","article-title":"Mitochondria damage checkpoint in apoptosis and genome stability","volume":"5","author":"Singh","year":"2004","journal-title":"FEMS Yeast Res"},{"key":"2026070714090036500_bib43","doi-asserted-by":"crossref","DOI":"10.1016\/j.jim.2019.112665","article-title":"Impact of tissue enzymatic digestion on analysis of immune cells in mouse reproductive mucosa with a focus on \u03b3\u03b4 T cells","volume":"474","author":"Skulska","year":"2019","journal-title":"J Immunol Methods"},{"key":"2026070714090036500_bib44","doi-asserted-by":"crossref","first-page":"513","DOI":"10.3109\/02656736.2014.971446","article-title":"Reactive oxygen species, heat stress and oxidative-induced mitochondrial damage. A review","volume":"30","author":"Slimen","year":"2014","journal-title":"Int J Hyperthermia"},{"key":"2026070714090036500_bib45","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1038\/nature11986","article-title":"Succinate is an inflammatory signal that induces IL-1\u03b2 through HIF-1\u03b1","volume":"496","author":"Tannahill","year":"2013","journal-title":"Nature"},{"key":"2026070714090036500_bib49","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1093\/biolre\/ioae180","article-title":"Inflammation during oocyte maturation reduces developmental competence and increases apoptosis in blastocysts","volume":"112","author":"Tariq","year":"2025","journal-title":"Biol Reprod"},{"key":"2026070714090036500_bib46","doi-asserted-by":"crossref","first-page":"1453","DOI":"10.1210\/en.2013-1822","article-title":"Epithelial and stromal cells of bovine endometrium have roles in innate immunity and initiate inflammatory responses to bacterial lipopeptides in vitro via toll-like receptors TLR2, TLR1, and TLR6","volume":"155","author":"Turner","year":"2014","journal-title":"Endocrinology"},{"key":"2026070714090036500_bib48","doi-asserted-by":"crossref","first-page":"809","DOI":"10.3168\/jds.S0022-0302(88)79621-6","article-title":"Dry period heat stress relief effects on prepartum progesterone, calf birth weight, and milk production","volume":"71","author":"Wolfenson","year":"1988","journal-title":"J Dairy Sci"},{"key":"2026070714090036500_bib47","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1111\/j.1365-2567.2004.02112.x","article-title":"Heat shock up-regulates expression of toll-like receptor-2 and toll-like receptor-4 in human monocytes via p38 kinase signal pathway","volume":"114","author":"Zhou","year":"2005","journal-title":"Immunology"}],"container-title":["Reproduction and Fertility"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/raf.bioscientifica.com\/view\/journals\/raf\/7\/1\/RAF-25-0213.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/raf.bioscientifica.com\/downloadpdf\/journals\/raf\/7\/1\/RAF-25-0213.xml","content-type":"text\/html","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/journals.bioscientifica.com\/raf\/article-pdf\/doi\/10.1530\/RAF-25-0213\/507533\/raf-25-0213.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/journals.bioscientifica.com\/raf\/article-pdf\/doi\/10.1530\/RAF-25-0213\/507533\/raf-25-0213.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T18:09:14Z","timestamp":1783447754000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.bioscientifica.com\/raf\/article\/7\/1\/RAF250213\/75973\/Heat-shock-suppresses-the-innate-immune-response"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,1]]},"references-count":51,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1,1]]}},"URL":"https:\/\/doi.org\/10.1530\/raf-25-0213","relation":{},"ISSN":["2633-8386"],"issn-type":[{"value":"2633-8386","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,1]]},"article-number":"RAF250213"}}