{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T02:42:31Z","timestamp":1787020951097,"version":"build-2736575974"},"reference-count":67,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,3,30]],"date-time":"2020-03-30T00:00:00Z","timestamp":1585526400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2020,3,30]],"date-time":"2020-03-30T00:00:00Z","timestamp":1585526400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010788","name":"Genome Prairie","doi-asserted-by":"publisher","award":["20110001"],"award-info":[{"award-number":["20110001"]}],"id":[{"id":"10.13039\/501100010788","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010788","name":"Genome Prairie","doi-asserted-by":"publisher","award":["20150329"],"award-info":[{"award-number":["20150329"]}],"id":[{"id":"10.13039\/501100010788","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008762","name":"Genome Canada","doi-asserted-by":"publisher","award":["C5208"],"award-info":[{"award-number":["C5208"]}],"id":[{"id":"10.13039\/100008762","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008762","name":"Genome Canada","doi-asserted-by":"publisher","award":["345169"],"award-info":[{"award-number":["345169"]}],"id":[{"id":"10.13039\/100008762","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Ontario Pork Producers Marketing Board","award":["17-011"],"award-info":[{"award-number":["17-011"]}]},{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","award":["CRDPJ-529583-18"],"award-info":[{"award-number":["CRDPJ-529583-18"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Vet Res"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>To better understand the host response to porcine reproductive and respiratory virus-2 (PRRSV2) we evaluated circulating thyroid hormone and associated gene expression in a late gestation challenge model. Pregnant gilts were inoculated at gestation day 85 and fetal samples collected at either 12 or 21\u00a0days post-infection (dpi). A subset of fetuses was selected for analysis based on viability and viral load categorized as either uninfected-viable (UNIF), high viral load viable (HV-VIA) or high viral load meconium stained (HV-MEC) and were compared with gestational age matched controls (CON). In dams, circulating levels of total T3 and T4 decreased in the acute period following infection and rebounded by 21 dpi. A similar effect was observed in fetuses, but was largely restricted to HV-VIA and HV-MEC, with minimal decrease noted in UNIF relative to CON at 21 dpi. Gene expression in fetal heart at 12 dpi showed significant decompensatory transcription of thyroid hormone transporters (SLC16A2) and deiodinases (DIO2, DIO3), which was not observed in brain. Correspondingly, genes associated with cell cycle progression (CDK1,2,4) were downregulated in only the heart of highly infected fetuses, while expression of their inhibitor (CDKN1A) was upregulated in both tissues. Finally, expression of genes associated with cardiac stress including CAMKD and AGT were upregulated in the hearts of highly infected fetuses, and a shift in expression of MYH6 to MYH7 was observed in HV-MEC fetuses specifically. Collectively, the results suggest PRRSV2 infection causes a hypothyroid state that disproportionally impacts the fetal heart over the brain.<\/jats:p>","DOI":"10.1186\/s13567-020-00772-2","type":"journal-article","created":{"date-parts":[[2020,3,30]],"date-time":"2020-03-30T13:02:42Z","timestamp":1585573362000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Maternal and fetal thyroid dysfunction following porcine reproductive and respiratory syndrome virus2 infection"],"prefix":"10.1186","volume":"51","author":[{"given":"J. Alex","family":"Pasternak","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel J.","family":"MacPhee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John C. S.","family":"Harding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,3,30]]},"reference":[{"key":"772_CR1","doi-asserted-by":"publisher","first-page":"154883","DOI":"10.1016\/j.cyto.2019.154883","volume":"126","author":"J Alex Pasternak","year":"2020","unstructured":"Alex Pasternak J, MacPhee DJ, Harding JCS (2020) Fetal cytokine response to porcine reproductive and respiratory syndrome virus-2 infection. Cytokine 126:154883","journal-title":"Cytokine"},{"key":"772_CR2","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1016\/j.virusres.2010.09.001","volume":"154","author":"RRR Rowland","year":"2010","unstructured":"Rowland RRR (2010) The interaction between PRRSV and the late gestation pig fetus. Virus Res 154:114\u2013122","journal-title":"Virus Res"},{"key":"772_CR3","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1186\/s13567-014-0113-8","volume":"45","author":"A Ladinig","year":"2014","unstructured":"Ladinig A, Lunney JK, Souza CJH, Ashley C, Plastow G, Harding JCS (2014) Cytokine profiles in pregnant gilts experimentally infected with porcine reproductive and respiratory syndrome virus and relationships with viral load and fetal outcome. Vet Res 45:113","journal-title":"Vet Res"},{"key":"772_CR4","doi-asserted-by":"publisher","first-page":"e0151198","DOI":"10.1371\/journal.pone.0151198","volume":"11","author":"P Novakovic","year":"2016","unstructured":"Novakovic P, Harding JCS, Al-Dissi AN, Ladinig A, Detmer SE (2016) Pathologic evaluation of type 2 porcine reproductive and respiratory syndrome virus infection at the maternal-fetal interface of late gestation pregnant gilts. PLoS One 11:e0151198","journal-title":"PLoS One"},{"key":"772_CR5","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1152\/physrev.00030.2013","volume":"94","author":"R Mullur","year":"2014","unstructured":"Mullur R, Liu Y-Y, Brent GA (2014) Thyroid hormone regulation of metabolism. Physiol Rev 94:355\u2013382","journal-title":"Physiol Rev"},{"key":"772_CR6","doi-asserted-by":"publisher","first-page":"306510","DOI":"10.4061\/2011\/306510","volume":"2011","author":"A Amin","year":"2011","unstructured":"Amin A, Dhillo WS, Murphy KG (2011) The central effects of thyroid hormones on appetite. J Thyroid Res 2011:306510","journal-title":"J Thyroid Res"},{"key":"772_CR7","doi-asserted-by":"publisher","first-page":"R87","DOI":"10.1530\/JOE-14-0025","volume":"221","author":"AJ Forhead","year":"2014","unstructured":"Forhead AJ, Fowden AL (2014) Thyroid hormones in fetal growth and prepartum maturation. J Endocrinol 221:R87\u2013R103","journal-title":"J Endocrinol"},{"key":"772_CR8","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1677\/joe.0.1550295","volume":"155","author":"E Krysin","year":"1997","unstructured":"Krysin E, Brzezi\u0144ska-Slebodzi\u0144ska E, Slebodzi\u0144ski AB (1997) Divergent deiodination of thyroid hormones in the separated parts of the fetal and maternal placenta in pigs. J Endocrinol 155:295\u2013303","journal-title":"J Endocrinol"},{"key":"772_CR9","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1556\/AVet.52.2004.4.1","volume":"52","author":"E Brzezi\u0144ska-Slebodzi\u0144ska","year":"2004","unstructured":"Brzezi\u0144ska-Slebodzi\u0144ska E, Slebodzi\u0144ski AB (2004) Changes in thyroxine, 3,3\u2032,5-triiodothyronine and 3,3\u20325\u2032-triiodothyronine content in the thyroid gland and in serum to thyroid tissue iodothyronine ratios during ontogenesis in the fetal pig. Acta Vet Hung 52:379\u2013387","journal-title":"Acta Vet Hung"},{"key":"772_CR10","doi-asserted-by":"publisher","first-page":"163","DOI":"10.3389\/fendo.2017.00163","volume":"8","author":"A Chatzitomaris","year":"2017","unstructured":"Chatzitomaris A, Hoermann R, Midgley JE, Hering S, Urban A, Dietrich B, Abood A, Klein HH, Dietrich JW (2017) Thyroid allostasis-adaptive responses of thyrotropic feedback control to conditions of strain, stress, and developmental programming. Front Endocrinol 8:163","journal-title":"Front Endocrinol"},{"key":"772_CR11","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1677\/JOE-09-0412","volume":"205","author":"MH Warner","year":"2010","unstructured":"Warner MH, Beckett GJ (2010) Mechanisms behind the non-thyroidal illness syndrome: an update. J Endocrinol 205:1\u201313","journal-title":"J Endocrinol"},{"key":"772_CR12","doi-asserted-by":"publisher","first-page":"1546","DOI":"10.1093\/jn\/108.9.1546","volume":"108","author":"T Atinmo","year":"1978","unstructured":"Atinmo T, Baldijao C, Pond WG, Barnes RH (1978) The effect of dietary protein restriction on serum thyroxine levels of pregnant or growing swine. J Nutr 108:1546\u20131553","journal-title":"J Nutr"},{"key":"772_CR13","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1016\/j.virusres.2018.12.002","volume":"260","author":"CM Malgarin","year":"2019","unstructured":"Malgarin CM, Nosach R, Novakovic P, Suleman M, Ladinig A, Detmer SE, MacPhee DJ, Harding JCS (2019) Classification of fetal resilience to porcine reproductive and respiratory syndrome (PRRS) based on temporal viral load in late gestation maternal tissues and fetuses. Virus Res 260:151\u2013162","journal-title":"Virus Res"},{"key":"772_CR14","doi-asserted-by":"publisher","first-page":"e109541","DOI":"10.1371\/journal.pone.0109541","volume":"9","author":"A Ladinig","year":"2014","unstructured":"Ladinig A, Foxcroft G, Ashley C, Lunney JK, Plastow G, Harding JCS (2014) Birth weight, intrauterine growth retardation and fetal susceptibility to porcine reproductive and respiratory syndrome virus. PLoS One 9:e109541","journal-title":"PLoS One"},{"key":"772_CR15","doi-asserted-by":"publisher","first-page":"e96104","DOI":"10.1371\/journal.pone.0096104","volume":"9","author":"A Ladinig","year":"2014","unstructured":"Ladinig A, Wilkinson J, Ashley C, Detmer SE, Lunney JK, Plastow G, Harding JCS (2014) Variation in fetal outcome, viral load and ORF5 sequence mutations in a large scale study of phenotypic responses to late gestation exposure to type 2 porcine reproductive and respiratory syndrome virus. PLoS One 9:e96104","journal-title":"PLoS One"},{"key":"772_CR16","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1016\/j.vetmic.2017.02.019","volume":"209","author":"JCS Harding","year":"2017","unstructured":"Harding JCS, Ladinig A, Novakovic P, Detmer SE, Wilkinson JM, Yang T, Lunney JK, Plastow GS (2017) Novel insights into host responses and reproductive pathophysiology of porcine reproductive and respiratory syndrome caused by PRRSV-2. Vet Microbiol 209:114\u2013123","journal-title":"Vet Microbiol"},{"key":"772_CR17","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1186\/s13567-015-0251-7","volume":"46","author":"A Ladinig","year":"2015","unstructured":"Ladinig A, Ashley C, Detmer SE, Wilkinson JM, Lunney JK, Plastow G, Harding JCS (2015) Maternal and fetal predictors of fetal viral load and death in third trimester, type 2 porcine reproductive and respiratory syndrome virus infected pregnant gilts. Vet Res 46:107","journal-title":"Vet Res"},{"key":"772_CR18","doi-asserted-by":"publisher","first-page":"931","DOI":"10.1067\/mob.2001.116828","volume":"185","author":"A Ghidini","year":"2001","unstructured":"Ghidini A, Spong CY (2001) Severe meconium aspiration syndrome is not caused by aspiration of meconium. Am J Obstet Gynecol 185:931\u2013938","journal-title":"Am J Obstet Gynecol"},{"key":"772_CR19","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1177\/104063870501700211","volume":"17","author":"SB Kleiboeker","year":"2005","unstructured":"Kleiboeker SB, Schommer SK, Lee S-M, Watkins S, Chittick W, Polson D (2005) Simultaneous detection of North American and European porcine reproductive and respiratory syndrome virus using real-time quantitative reverse transcriptase-PCR. J Vet Diagn Invest 17:165\u2013170","journal-title":"J Vet Diagn Invest"},{"key":"772_CR20","first-page":"3914","volume":"95","author":"NM Chapel","year":"2017","unstructured":"Chapel NM, Byrd CJ, Lugar DW, Morello GM, Baumgard LH, Ross JW, Safranski TJ, Lucy MC, Johnson JS (2017) Determining the effects of early gestation in utero heat stress on postnatal fasting heat production and circulating biomarkers associated with metabolism in growing pigs. J Anim Sci 95:3914\u20133921","journal-title":"J Anim Sci"},{"key":"772_CR21","doi-asserted-by":"publisher","first-page":"7556","DOI":"10.3168\/jds.2019-16294","volume":"102","author":"C Kent-Dennis","year":"2019","unstructured":"Kent-Dennis C, Pasternak A, Plaizier JC, Penner GB (2019) Potential for a localized immune response by the ruminal epithelium in nonpregnant heifers following a short-term subacute ruminal acidosis challenge. J Dairy Sci 102:7556\u20137569","journal-title":"J Dairy Sci"},{"key":"772_CR22","volume-title":"R: A Language and Environment for Statistical Computing","author":"R Core Team","year":"2019","unstructured":"R Core Team (2019) R: A Language and Environment for Statistical Computing. R Core Team, Vienna"},{"key":"772_CR23","unstructured":"Pinheiro J, Bates D, DebRoy S, SarKar D (2019) nlme: linear and nonlinear mixed effects models. https:\/\/cran.r-project.org\/web\/packages\/nlme\/citation.html"},{"key":"772_CR24","unstructured":"Lenth R (2019) emmeans: estimated marginal means, aka least-squares means"},{"key":"772_CR25","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-24277-4","volume-title":"ggplot2: elegant graphics for data analysis","author":"H Wickham","year":"2016","unstructured":"Wickham H (2016) ggplot2: elegant graphics for data analysis. Springer, New York"},{"key":"772_CR26","doi-asserted-by":"publisher","first-page":"385","DOI":"10.2460\/javma.2005.227.385","volume":"227","author":"EJ Neumann","year":"2005","unstructured":"Neumann EJ, Kliebenstein JB, Johnson CD, Mabry JW, Bush EJ, Seitzinger AH, Green AL, Zimmerman JJ (2005) Assessment of the economic impact of porcine reproductive and respiratory syndrome on swine production in the United States. J Am Vet Med Assoc 227:385\u2013392","journal-title":"J Am Vet Med Assoc"},{"key":"772_CR27","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/S0021-9258(18)86585-1","volume":"33","author":"EB Hart","year":"1918","unstructured":"Hart EB, Steenbock H (1918) Thyroid hyperplasia and the relation of iodine to the Hairless Pig Malady. J Biol Chem 33:313","journal-title":"J Biol Chem"},{"key":"772_CR28","doi-asserted-by":"publisher","first-page":"755","DOI":"10.2527\/1991.692755x","volume":"69","author":"FC Buonomo","year":"1991","unstructured":"Buonomo FC, Baile CA (1991) Influence of nutritional deprivation on insulin-like growth factor I, somatotropin, and metabolic hormones in swine. J Anim Sci 69:755\u2013760","journal-title":"J Anim Sci"},{"key":"772_CR29","doi-asserted-by":"publisher","first-page":"1035","DOI":"10.1016\/0031-9384(86)90476-2","volume":"36","author":"M Macari","year":"1986","unstructured":"Macari M, Zuim SM, Secato ER, Guerreiro JR (1986) Effects of ambient temperature and thyroid hormones on food intake by pigs. Physiol Behav 36:1035\u20131039","journal-title":"Physiol Behav"},{"key":"772_CR30","doi-asserted-by":"publisher","first-page":"1025","DOI":"10.1007\/s11250-018-1526-6","volume":"50","author":"PK Pathak","year":"2018","unstructured":"Pathak PK, Roychoudhury R, Saharia J, Borah MC, Dutta DJ, Bhuyan R, Kalita D (2018) Impact of seasonal thermal stress on physiological and blood biochemical parameters in pigs under different dietary energy levels. Trop Anim Health Prod 50:1025\u20131032","journal-title":"Trop Anim Health Prod"},{"key":"772_CR31","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1016\/S0739-7240(98)00006-X","volume":"15","author":"JA Carroll","year":"1998","unstructured":"Carroll JA, Veum TL, Matteri RL (1998) Endocrine responses to weaning and changes in post-weaning diet in the young pig. Domest Anim Endocrinol 15:183\u2013194","journal-title":"Domest Anim Endocrinol"},{"key":"772_CR32","doi-asserted-by":"publisher","first-page":"2534","DOI":"10.2527\/2004.8292534x","volume":"82","author":"RL McPherson","year":"2004","unstructured":"McPherson RL, Ji F, Wu G, Blanton JR, Kim SW (2004) Growth and compositional changes of fetal tissues in pigs. J Anim Sci 82:2534\u20132540","journal-title":"J Anim Sci"},{"key":"772_CR33","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1016\/0300-9629(89)90068-6","volume":"93","author":"GS Spencer","year":"1989","unstructured":"Spencer GS, Hallett KG, Beermann U, Macdonald AA (1989) Changes in the levels of growth hormones, insulin, cortisol, thyroxine and somatomedin-C\/IGF-1, with increasing gestational age in the fetal pig, and the effect of thyroidectomy in utero. Comp Biochem Physiol Comp Physiol 93:467\u2013472","journal-title":"Comp Biochem Physiol Comp Physiol"},{"key":"772_CR34","first-page":"R1300","volume":"261","author":"DI Finkelstein","year":"1991","unstructured":"Finkelstein DI, Andrianakis P, Luff AR, Walker D (1991) Effects of thyroidectomy on development of skeletal muscle in fetal sheep. Am J Physiol 261:R1300\u20131306","journal-title":"Am J Physiol"},{"key":"772_CR35","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1096\/fj.10-179895","volume":"26","author":"NN Chattergoon","year":"2012","unstructured":"Chattergoon NN, Giraud GD, Louey S, Stork P, Fowden AL, Thornburg KL (2012) Thyroid hormone drives fetal cardiomyocyte maturation. FASEB J 26:397\u2013408","journal-title":"FASEB J"},{"key":"772_CR36","doi-asserted-by":"publisher","first-page":"278","DOI":"10.1016\/0002-9378(77)90469-0","volume":"127","author":"A Bhakthavathsalan","year":"1977","unstructured":"Bhakthavathsalan A, Mann LI, Ayromlooi J, Kunzel W, Liu M (1977) The effects of fetal thyroidectomy in the ovine fetus. Am J Obstet Gynecol 127:278\u2013284","journal-title":"Am J Obstet Gynecol"},{"key":"772_CR37","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1677\/joe.0.1270341","volume":"127","author":"TA Yarney","year":"1990","unstructured":"Yarney TA, Kendall JZ, Randall GC (1990) Cytosolic glucocorticoid receptors in the porcine lung during development and after hypophysectomy or thyroidectomy. J Endocrinol 127:341\u2013349","journal-title":"J Endocrinol"},{"key":"772_CR38","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1016\/j.micpath.2011.04.001","volume":"51","author":"UU Karniychuk","year":"2011","unstructured":"Karniychuk UU, Saha D, Geldhof M, Vanhee M, Cornillie P, Van den Broeck W, Nauwynck HJ (2011) Porcine reproductive and respiratory syndrome virus (PRRSV) causes apoptosis during its replication in fetal implantation sites. Microb Pathog 51:194\u2013202","journal-title":"Microb Pathog"},{"key":"772_CR39","doi-asserted-by":"crossref","first-page":"12628","DOI":"10.1016\/S0021-9258(18)90792-1","volume":"259","author":"RA Chizzonite","year":"1984","unstructured":"Chizzonite RA, Zak R (1984) Regulation of myosin isoenzyme composition in fetal and neonatal rat ventricle by endogenous thyroid hormones. J Biol Chem 259:12628\u201312632","journal-title":"J Biol Chem"},{"key":"772_CR40","doi-asserted-by":"publisher","first-page":"1008","DOI":"10.1016\/j.steroids.2007.12.016","volume":"73","author":"JL Leonard","year":"2008","unstructured":"Leonard JL (2008) Non-genomic actions of thyroid hormone in brain development. Steroids 73:1008\u20131012","journal-title":"Steroids"},{"key":"772_CR41","doi-asserted-by":"publisher","first-page":"230","DOI":"10.1172\/JCI123176","volume":"129","author":"S Jo","year":"2019","unstructured":"Jo S, Fonseca TL, Bocco BMLC, Fernandes GW, McAninch EA, Bolin AP, Da Concei\u00e7\u00e3o RR, Werneck-de-Castro JP, Ignacio DL, Egri P, N\u00e9meth D, Fekete C, Bernardi MM, Leitch VD, Mannan NS, Curry KF, Butterfield NC, Bassett JHD, Williams GR, Gereben B, Ribeiro MO, Bianco AC (2019) Type 2 deiodinase polymorphism causes ER stress and hypothyroidism in the brain. J Clin Invest 129:230\u2013245","journal-title":"J Clin Invest"},{"key":"772_CR42","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1530\/JOE-11-0002","volume":"209","author":"M Dentice","year":"2011","unstructured":"Dentice M, Salvatore D (2011) Deiodinases: the balance of thyroid hormone: local impact of thyroid hormone inactivation. J Endocrinol 209:273\u2013282","journal-title":"J Endocrinol"},{"key":"772_CR43","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1016\/j.mce.2016.07.037","volume":"437","author":"AA van Mullem","year":"2016","unstructured":"van Mullem AA, van Gucht ALM, Visser WE, Meima ME, Peeters RP, Visser TJ (2016) Effects of thyroid hormone transporters MCT8 and MCT10 on nuclear activity of T3. Mol Cell Endocrinol 437:252\u2013260","journal-title":"Mol Cell Endocrinol"},{"key":"772_CR44","doi-asserted-by":"publisher","first-page":"5267","DOI":"10.1210\/endo.140.11.7145","volume":"140","author":"G Barrera-Hernandez","year":"1999","unstructured":"Barrera-Hernandez G, Park KS, Dace A, Zhan Q, Cheng SY (1999) Thyroid hormone-induced cell proliferation in GC cells is mediated by changes in G1 cyclin\/cyclin-dependent kinase levels and activity. Endocrinology 140:5267\u20135274","journal-title":"Endocrinology"},{"key":"772_CR45","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1016\/j.jsbmb.2007.12.008","volume":"109","author":"LC Hall","year":"2008","unstructured":"Hall LC, Salazar EP, Kane SR, Liu N (2008) Effects of thyroid hormones on human breast cancer cell proliferation. J Steroid Biochem Mol Biol 109:57\u201366","journal-title":"J Steroid Biochem Mol Biol"},{"key":"772_CR46","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1159\/000486850","volume":"40","author":"AM Antonson","year":"2018","unstructured":"Antonson AM, Balakrishnan B, Radlowski EC, Petr G, Johnson RW (2018) Altered hippocampal gene expression and morphology in fetal piglets following maternal respiratory viral infection. Dev Neurosci 40:104\u2013119","journal-title":"Dev Neurosci"},{"key":"772_CR47","doi-asserted-by":"publisher","first-page":"R1","DOI":"10.1677\/JOE-06-0114","volume":"192","author":"NN Chattergoon","year":"2007","unstructured":"Chattergoon NN, Giraud GD, Thornburg KL (2007) Thyroid hormone inhibits proliferation of fetal cardiac myocytes in vitro. J Endocrinol 192:R1\u20138","journal-title":"J Endocrinol"},{"key":"772_CR48","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1016\/j.mce.2009.08.028","volume":"313","author":"E Kress","year":"2009","unstructured":"Kress E, Samarut J, Plateroti M (2009) Thyroid hormones and the control of cell proliferation or cell differentiation: paradox or duality? Mol Cell Endocrinol 313:36\u201349","journal-title":"Mol Cell Endocrinol"},{"key":"772_CR49","doi-asserted-by":"publisher","first-page":"6043","DOI":"10.1073\/pnas.0601072103","volume":"103","author":"MG Trivieri","year":"2006","unstructured":"Trivieri MG, Oudit GY, Sah R, Kerfant B-G, Sun H, Gramolini AO, Pan Y, Wickenden AD, Croteau W, Morreale de Escobar G, Pekhletski R, St Germain D, Maclennan DH, Backx PH (2006) Cardiac-specific elevations in thyroid hormone enhance contractility and prevent pressure overload-induced cardiac dysfunction. Proc Natl Acad Sci U S A 103:6043\u20136048","journal-title":"Proc Natl Acad Sci U S A"},{"key":"772_CR50","doi-asserted-by":"publisher","first-page":"1053","DOI":"10.1006\/jmcc.2001.1366","volume":"33","author":"M Periasamy","year":"2001","unstructured":"Periasamy M, Huke S (2001) SERCA pump level is a critical determinant of Ca(2\u2009+)homeostasis and cardiac contractility. J Mol Cell Cardiol 33:1053\u20131063","journal-title":"J Mol Cell Cardiol"},{"key":"772_CR51","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/S1054-3589(10)59001-X","volume":"59","author":"A Kushnir","year":"2010","unstructured":"Kushnir A, Marks AR (2010) The ryanodine receptor in cardiac physiology and disease. Adv Pharmacol 59:1\u201330","journal-title":"Adv Pharmacol"},{"key":"772_CR52","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1007\/978-3-319-55858-5_5","volume":"981","author":"PA Gorski","year":"2017","unstructured":"Gorski PA, Ceholski DK, Young HS (2017) Structure-function relationship of the SERCA Pump and its regulation by phospholamban and sarcolipin. Adv Exp Med Biol 981:77\u2013119","journal-title":"Adv Exp Med Biol"},{"key":"772_CR53","doi-asserted-by":"publisher","first-page":"582","DOI":"10.1590\/2359-3997000000208","volume":"60","author":"FV Campanha","year":"2016","unstructured":"Campanha FV, Perone D, Campos DH, Luvizotto RA, De S\u00edbio MT, Oliveira M, Olimpio RM, Moretto FC, Padovani CR, Mazeto GM, Cicogna AC, Nogueira CR (2016) Thyroxine increases Serca2 and Ryr2 gene expression in heart failure rats with euthyroid sick syndrome. Arch Endocrinol Metab 60:582\u2013586","journal-title":"Arch Endocrinol Metab"},{"key":"772_CR54","doi-asserted-by":"publisher","first-page":"H943","DOI":"10.1152\/ajpheart.00490.2010","volume":"300","author":"R Vetter","year":"2011","unstructured":"Vetter R, Rehfeld U, Reissfelder C, Fechner H, Seppet E, Kreutz R (2011) Decreased cardiac SERCA2 expression, SR Ca uptake, and contractile function in hypothyroidism are attenuated in SERCA2 overexpressing transgenic rats. Am J Physiol Heart Circ Physiol 300:H943\u2013950","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"772_CR55","doi-asserted-by":"publisher","first-page":"2946","DOI":"10.1210\/en.2009-1241","volume":"151","author":"M Belakavadi","year":"2010","unstructured":"Belakavadi M, Saunders J, Weisleder N, Raghava PS, Fondell JD (2010) Repression of cardiac phospholamban gene expression is mediated by thyroid hormone receptor-\u03b11 and involves targeted covalent histone modifications. Endocrinology 151:2946\u20132956","journal-title":"Endocrinology"},{"key":"772_CR56","doi-asserted-by":"publisher","first-page":"713","DOI":"10.1161\/01.RES.84.6.713","volume":"84","author":"B Hoch","year":"1999","unstructured":"Hoch B, Meyer R, Hetzer R, Krause EG, Karczewski P (1999) Identification and expression of delta-isoforms of the multifunctional Ca2\u2009+\/calmodulin-dependent protein kinase in failing and nonfailing human myocardium. Circ Res 84:713\u2013721","journal-title":"Circ Res"},{"key":"772_CR57","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1007\/s10741-015-9498-3","volume":"20","author":"L Daniels","year":"2015","unstructured":"Daniels L, Bell JR, Delbridge LMD, McDonald FJ, Lamberts RR, Erickson JR (2015) The role of CaMKII in diabetic heart dysfunction. Heart Fail Rev 20:589\u2013600","journal-title":"Heart Fail Rev"},{"key":"772_CR58","doi-asserted-by":"publisher","first-page":"2342","DOI":"10.1073\/pnas.0813013106","volume":"106","author":"J Backs","year":"2009","unstructured":"Backs J, Backs T, Neef S, Kreusser MM, Lehmann LH, Patrick DM, Grueter CE, Qi X, Richardson JA, Hill JA, Katus HA, Bassel-Duby R, Maier LS, Olson EN (2009) The delta isoform of CaM kinase II is required for pathological cardiac hypertrophy and remodeling after pressure overload. Proc Natl Acad Sci U S A 106:2342\u20132347","journal-title":"Proc Natl Acad Sci U S A"},{"key":"772_CR59","doi-asserted-by":"publisher","first-page":"935","DOI":"10.1161\/CIRCRESAHA.112.276915","volume":"112","author":"H Ling","year":"2013","unstructured":"Ling H, Gray CBB, Zambon AC, Grimm M, Gu Y, Dalton N, Purcell NH, Peterson K, Brown JH (2013) Ca2\u2009+\/Calmodulin-dependent protein kinase II \u03b4 mediates myocardial ischemia\/reperfusion injury through nuclear factor-\u03baB. Circ Res 112:935\u2013944","journal-title":"Circ Res"},{"key":"772_CR60","doi-asserted-by":"publisher","first-page":"507","DOI":"10.1002\/j.1460-2075.1992.tb05081.x","volume":"11","author":"MD Planas-Silva","year":"1992","unstructured":"Planas-Silva MD, Means AR (1992) Expression of a constitutive form of calcium\/calmodulin dependent protein kinase II leads to arrest of the cell cycle in G2. EMBO J 11:507\u2013517","journal-title":"EMBO J"},{"key":"772_CR61","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1016\/j.vph.2009.10.009","volume":"52","author":"MLM Barreto-Chaves","year":"2010","unstructured":"Barreto-Chaves MLM, Carrillo-Sep\u00falveda MA, Carneiro-Ramos MS, Gomes DA, Diniz GP (2010) The crosstalk between thyroid hormones and the renin-angiotensin system. Vascul Pharmacol 52:166\u2013170","journal-title":"Vascul Pharmacol"},{"key":"772_CR62","doi-asserted-by":"publisher","first-page":"C838","DOI":"10.1152\/ajpcell.1992.263.4.C838","volume":"263","author":"DE Dostal","year":"1992","unstructured":"Dostal DE, Rothblum KN, Chernin MI, Cooper GR, Baker KM (1992) Intracardiac detection of angiotensinogen and renin: a localized renin-angiotensin system in neonatal rat heart. Am J Physiol 263:C838\u2013850","journal-title":"Am J Physiol"},{"key":"772_CR63","doi-asserted-by":"publisher","first-page":"770","DOI":"10.1016\/j.yjmcc.2008.09.121","volume":"45","author":"H Lal","year":"2008","unstructured":"Lal H, Verma SK, Golden HB, Foster DM, Smith M, Dostal DE (2008) Stretch-induced regulation of angiotensinogen gene expression in cardiac myocytes and fibroblasts: opposing roles of JNK1\/2 and p38alpha MAP kinases. J Mol Cell Cardiol 45:770\u2013778","journal-title":"J Mol Cell Cardiol"},{"key":"772_CR64","doi-asserted-by":"publisher","first-page":"15058","DOI":"10.1021\/bi0495329","volume":"43","author":"UP Malmqvist","year":"2004","unstructured":"Malmqvist UP, Aronshtam A, Lowey S (2004) Cardiac myosin isoforms from different species have unique enzymatic and mechanical properties. Biochemistry 43:15058\u201315065","journal-title":"Biochemistry"},{"key":"772_CR65","doi-asserted-by":"publisher","first-page":"388","DOI":"10.1016\/j.yjmcc.2007.07.045","volume":"43","author":"MP Gupta","year":"2007","unstructured":"Gupta MP (2007) Factors controlling cardiac myosin-isoform shift during hypertrophy and heart failure. J Mol Cell Cardiol 43:388\u2013403","journal-title":"J Mol Cell Cardiol"},{"key":"772_CR66","doi-asserted-by":"publisher","first-page":"H1968","DOI":"10.1152\/ajpheart.00644.2010","volume":"299","author":"F Haddad","year":"2010","unstructured":"Haddad F, Jiang W, Bodell PW, Qin AX, Baldwin KM (2010) Cardiac myosin heavy chain gene regulation by thyroid hormone involves altered histone modifications. Am J Physiol Heart Circ Physiol 299:H1968\u20131980","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"772_CR67","doi-asserted-by":"publisher","first-page":"2315","DOI":"10.1172\/JCI119770","volume":"100","author":"BD Lowes","year":"1997","unstructured":"Lowes BD, Minobe W, Abraham WT, Rizeq MN, Bohlmeyer TJ, Quaife RA, Roden RL, Dutcher DL, Robertson AD, Voelkel NF, Badesch DB, Groves BM, Gilbert EM, Bristow MR (1997) Changes in gene expression in the intact human heart. Downregulation of alpha-myosin heavy chain in hypertrophied, failing ventricular myocardium. J Clin Invest 100:2315\u20132324","journal-title":"J Clin Invest"}],"container-title":["Veterinary Research"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s13567-020-00772-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s13567-020-00772-2\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s13567-020-00772-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,3,29]],"date-time":"2021-03-29T19:09:45Z","timestamp":1617044985000},"score":1,"resource":{"primary":{"URL":"https:\/\/veterinaryresearch.biomedcentral.com\/articles\/10.1186\/s13567-020-00772-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,3,30]]},"references-count":67,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,12]]}},"alternative-id":["772"],"URL":"https:\/\/doi.org\/10.1186\/s13567-020-00772-2","relation":{},"ISSN":["1297-9716"],"issn-type":[{"value":"1297-9716","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,3,30]]},"assertion":[{"value":"4 January 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 March 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 March 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Animal work was conducted in strict accordance with the guidelines of the Canadian Council of Animal Care and with approval of the University of Saskatchewan\u2019s Animal Research Ethics Board (Exp. 1 Protocol # 20110102, Exp. 2 Protocol # 20160023).","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"The authors declare that they have no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"47"}}