{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T21:56:46Z","timestamp":1768514206589,"version":"3.49.0"},"reference-count":44,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,5,1]],"date-time":"2021-05-01T00:00:00Z","timestamp":1619827200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,5,1]],"date-time":"2021-05-01T00:00:00Z","timestamp":1619827200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Vet Res"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Mechanisms of fetal death following maternal PRRSV2 infection remain uncharacterized, although hypoxia from umbilical cord lesions and\/or placental detachment due to apoptosis are hypothesized. We performed two experiments examining hypoxia and apoptosis in PRRSV-infected and non-infected, third-trimester fetuses to elucidate possible associations with fetal death. Fetuses were selected based on four phenotypic infection groups: fetuses from non-challenged control gilts (CTRL); low viral load fetuses (LVL; Exp 1) or uninfected fetuses (UNINF; Exp 2) from inoculated gilts; viable high viral load fetuses (HVL-VIA); and HVL meconium-stained fetuses (HVL-MEC).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In experiment 1, paraffin embedded fetal tissues collected 21\u2009days post maternal infection (DPI) were examined for DNA fragmentation associated with apoptosis. Positively stained foci were larger and more numerous (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.05) in heart, liver, and thymus of HVL-VIA and HVL-MEC compared to CTRL and LVL fetuses. In experiment 2, group differences in gene expression within the hypoxia (HIF1a, IDO1, VEGFa, LDHA, NOS2, NOX1) and apoptosis (CASP3, CASP7, CASP8, CASP9, RIPK1, RIPK3) pathways were assessed by RT-qPCR in fetal tissues collected at 12 DPI. High viral load fetuses showed differential expression relative to the CTRL and UNINF (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.05 for all). Brain tissue from HVL-VIA and HVL-MEC fetuses presented increased expression of CASP7, CASP8, RIPK3, HIF1a and IDO1. Fetal heart showed increased expression of CASP8, HIF1a, IDO and NOX1 and a decrease in NOS2 expression in infected groups. CASP7, CASP9, RIPK1 and RIPK3 were only increased in the heart of HVL-VIA while VEGFa was only increased for HVL-MEC fetuses. Thymus from HVL-MEC had decreased expression of CASP9 and there was increased IDO1 in all infected fetuses.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>There is strong evidence of apoptosis occurring in the heart, liver and thymus of highly viral load fetuses at 21 DPI. Furthermore, there was clear upregulation of apoptotic genes in the heart of high viral load infected fetuses and less prominent upregulation in the brain of PRRSV-infected fetuses, whereas thymus appears to be spared at 12 DPI. There was no strong evidence of hypoxia at 12 DPI in brain and thymus but some indication of hypoxia occurring in fetal heart.<\/jats:p><\/jats:sec>","DOI":"10.1186\/s12917-021-02883-0","type":"journal-article","created":{"date-parts":[[2021,5,3]],"date-time":"2021-05-03T11:43:03Z","timestamp":1620042183000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Fetal hypoxia and apoptosis following maternal porcine reproductive and respiratory syndrome virus (PRRSV) infection"],"prefix":"10.1186","volume":"17","author":[{"given":"Carolina M.","family":"Malgarin","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fiona","family":"Moser","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. Alex","family":"Pasternak","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Glenn","family":"Hamonic","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susan E.","family":"Detmer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel J.","family":"MacPhee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John C. S.","family":"Harding","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,5,1]]},"reference":[{"issue":"2","key":"2883_CR1","doi-asserted-by":"crossref","first-page":"72","DOI":"10.54846\/jshap\/754","volume":"21","author":"DJ Holtkamp","year":"2013","unstructured":"Holtkamp DJ, Kliebenstein JB, Neumann EJ, Zimmerman JJ, Rotto HF, Yoder TK, et al. Assessment of the economic impact of porcine reproductive and respiratory syndrome virus on United States pork producers. J Swine Heal Prod. 2013;21(2):72\u201384.","journal-title":"J Swine Heal Prod"},{"issue":"10","key":"2883_CR2","doi-asserted-by":"crossref","first-page":"1391","DOI":"10.2460\/ajvr.1994.55.10.1391","volume":"55","author":"WL Mengeling","year":"1994","unstructured":"Mengeling WL, Lager KM, Vorwald AC. Temporal characterization of transplacental infection of porcine fetuses with porcine reproductive and respiratory syndrome virus. Am J Vet Res. 1994;55(10):1391\u20138.","journal-title":"Am J Vet Res"},{"issue":"1996","key":"2883_CR3","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1177\/104063879600800301","volume":"8","author":"KM Lager","year":"1996","unstructured":"Lager KM, Halbur PG. ERRADOGross and microscopic lesions in porcine fetuses infected with porcine reproductive and respiratory syndrome virus. J Vet Diagn Investig. 1996;8(1996):275\u201382.","journal-title":"J Vet Diagn Investig"},{"issue":"1","key":"2883_CR4","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1177\/030098589603300115","volume":"33","author":"KD Rossow","year":"1996","unstructured":"Rossow KD, Laube KL, Goyal SM, Collins JE. Fetal microscopic lesions in porcine reproductive and respiratory syndrome virus-induced abortion. Vet Pathol. 1996;33(1):95\u20139.","journal-title":"Vet Pathol"},{"issue":"5","key":"2883_CR5","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1093\/femspd\/fty060","volume":"76","author":"M Suleman","year":"2018","unstructured":"Suleman M, Novakovic P, Malgarin CM, Detmer SE, Harding JCS, MacPhee DJ. Spatiotemporal immunofluorescent evaluation of porcine reproductive and respiratory syndrome virus transmission across the maternal-fetal interface. Pathog Dis. 2018;76(5):1\u201314.","journal-title":"Pathog Dis"},{"key":"2883_CR6","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 SESE, et al. 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. 2019;260:151\u201362.","journal-title":"Virus Res"},{"key":"2883_CR7","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1016\/j.virusres.2015.03.005","volume":"203","author":"A Ladinig","year":"2015","unstructured":"Ladinig A, Detmer SE, Clarke K, Ashley C, Rowland RR, Lunney JK, et al. Pathogenicity of three type 2 porcine reproductive and respiratory syndrome virus strains in experimentally inoculated pregnant gilts. Virus Res. 2015;203:24\u201335.","journal-title":"Virus Res"},{"issue":"3","key":"2883_CR8","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. Pathologic evaluation of type 2 porcine reproductive and respiratory syndrome virus infection at the maternal-fetal interface of late gestation pregnant gilts. PLoS One. 2016;11(3):e0151198.","journal-title":"PLoS One"},{"issue":"3","key":"2883_CR9","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, et al. Porcine reproductive and respiratory syndrome virus (PRRSV) causes apoptosis during its replication in fetal implantation sites. Microb Pathog. 2011;51(3):194\u2013202.","journal-title":"Microb Pathog"},{"issue":"1\u20132","key":"2883_CR10","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1016\/j.virusres.2013.05.005","volume":"176","author":"UU Karniychuk","year":"2013","unstructured":"Karniychuk UU, De Spiegelaere W, Nauwynck HJ. Porcine reproductive and respiratory syndrome virus infection is associated with an increased number of Sn-positive and CD8-positive cells in the maternal-fetal interface. Virus Res. 2013;176(1\u20132):285\u201391.","journal-title":"Virus Res"},{"key":"2883_CR11","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, et al. 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. 2015;46:107.","journal-title":"Vet Res"},{"issue":"4","key":"2883_CR12","doi-asserted-by":"publisher","first-page":"521","DOI":"10.1177\/0300985818765067","volume":"55","author":"P Novakovic","year":"2018","unstructured":"Novakovic P, Detmer SE, Suleman M, Malgarin CM, MacPhee DJ, Harding JCS. Histologic changes associated with placental separation in gilts infected with porcine reproductive and respiratory syndrome virus. Vet Pathol. 2018;55(4):521\u201330.","journal-title":"Vet Pathol"},{"issue":"3","key":"2883_CR13","doi-asserted-by":"publisher","first-page":"e0173360","DOI":"10.1371\/journal.pone.0173360","volume":"12","author":"P Novakovic","year":"2017","unstructured":"Novakovic P, Harding JC, Al-Dissi AN, Detmer SE. Type 2 porcine reproductive and respiratory syndrome virus infection increases apoptosis at the maternal-fetal interface in late gestation pregnant gilts. PLoS One. 2017;12(3):e0173360.","journal-title":"PLoS One"},{"issue":"1996","key":"2883_CR14","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1177\/104063879600800301","volume":"8","author":"KM Lager","year":"1996","unstructured":"Lager KM, Halbur PG, Invest JVD. Gross and microscopic lesions in porcine fetuses infected with porcine reproductive and respiratory syndrome virus. J Vet Diagn Investig. 1996;8(1996):275\u201382.","journal-title":"J Vet Diagn Investig"},{"issue":"2","key":"2883_CR15","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1016\/S0092-8674(04)00046-7","volume":"116","author":"NN Danial","year":"2004","unstructured":"Danial NN, Korsmeyer SJ. Cell death: critical control points. Cell. 2004;116(2):205\u201319.","journal-title":"Cell."},{"key":"2883_CR16","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1186\/s12864-016-2720-4","volume":"17","author":"JM Wilkinson","year":"2016","unstructured":"Wilkinson JM, Bao H, Ladinig A, Hong L, Stothard P, Lunney JK, et al. Genome-wide analysis of the transcriptional response to porcine reproductive and respiratory syndrome virus infection at the maternal\/fetal interface and in the fetus. BMC Genomics. 2016;17:383.","journal-title":"BMC Genomics"},{"key":"2883_CR17","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. Fetal cytokine response to porcine reproductive and respiratory syndrome virus-2 infection. Cytokine. 2020;126:154883.","journal-title":"Cytokine."},{"key":"2883_CR18","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s13567-020-00772-2","volume":"51","author":"JA Pasternak","year":"2020","unstructured":"Pasternak JA, MacPhee DJ, Harding JCS. Maternal and fetal thyroid dysfunction following porcine reproductive and respiratory syndrome virus2 infection. Vet Res. 2020;51:1.","journal-title":"Vet Res"},{"issue":"1","key":"2883_CR19","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12864-020-07154-0","volume":"21","author":"A Van Goor","year":"2020","unstructured":"Van Goor A, Pasternak A, Walker K, Hong L, Malgarin C, MacPhee DJDJ, et al. Differential responses in placenta and fetal thymus at 12 days post infection elucidate mechanisms of viral level and fetal compromise following PRRSV2 infection. BMC Genomics. 2020;21(1):1\u201320.","journal-title":"BMC Genomics"},{"issue":"2","key":"2883_CR20","first-page":"10","volume":"2","author":"WT Christianson","year":"1994","unstructured":"Christianson WT, Joo HS. Porcine reproductive and respiratory syndrome: a review. Swine Heal Prod. 1994;2(2):10\u201328.","journal-title":"Swine Heal Prod"},{"key":"2883_CR21","volume-title":"Diseases of swine, [internet]. Diseases of swine","author":"RA Craig","year":"1906","unstructured":"Craig RA. Diseases of swine, [internet]. Diseases of swine. New York: O. Judd company; 1906."},{"issue":"6","key":"2883_CR22","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1016\/j.placenta.2009.03.016","volume":"30","author":"UU Karniychuk","year":"2009","unstructured":"Karniychuk UU, Nauwynck HJ. Quantitative changes of sialoadhesin and CD163 positive macrophages in the implantation sites and organs of porcine embryos\/fetuses during gestation. Placenta. 2009;30(6):497\u2013500.","journal-title":"Placenta."},{"issue":"1","key":"2883_CR23","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1186\/s13567-016-0364-7","volume":"47","author":"P Novakovic","year":"2016","unstructured":"Novakovic P, Harding JC, Ladinig A, Al-Dissi AN, MacPhee DJ, Detmer SE. Relationships of CD163 and CD169 positive cell numbers in the endometrium and fetal placenta with type 2 PRRSV RNA concentration in fetal thymus. Vet Res. 2016;47(1):76.","journal-title":"Vet Res"},{"issue":"1","key":"2883_CR24","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1186\/1297-9716-44-95","volume":"44","author":"UU Karniychuk","year":"2013","unstructured":"Karniychuk UU, Nauwynck HJ. Pathogenesis and prevention of placental and transplacental porcine reproductive and respiratory syndrome virus infection. Vet Res. 2013;44(1):95.","journal-title":"Vet Res"},{"issue":"4","key":"2883_CR25","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, et al. 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. 2014;9(4):e96104.","journal-title":"PLoS One"},{"issue":"1","key":"2883_CR26","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12974-018-1235-0","volume":"15","author":"YK Dhuriya","year":"2018","unstructured":"Dhuriya YK, Sharma D. Necroptosis: a regulated inflammatory mode of cell death. J Neuroinflammation. 2018;15(1):1\u20139.","journal-title":"J Neuroinflammation"},{"issue":"1\u20132","key":"2883_CR27","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1016\/j.virusres.2010.09.001","volume":"154","author":"RR Rowland","year":"2010","unstructured":"Rowland RR. The interaction between PRRSV and the late gestation pig fetus. Virus Res. 2010;154(1\u20132):114\u201322.","journal-title":"Virus Res"},{"issue":"6","key":"2883_CR28","doi-asserted-by":"publisher","first-page":"582","DOI":"10.1177\/104063870001200619","volume":"12","author":"D-S Cheon","year":"2000","unstructured":"Cheon D-S, Chae C. Comparison of virus isolation, reverse transcription-polymerase chain reaction, immunohistochemistry, and in situ hybridization for the detection of porcine reproductive and respiratory syndrome virus from naturally aborted fetuses and stillborn piglets. J Vet Diagn Investig. 2000;12(6):582\u20137.","journal-title":"J Vet Diagn Investig"},{"issue":"4","key":"2883_CR29","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1053\/jcpa.2000.0457","volume":"124","author":"DS Cheon","year":"2001","unstructured":"Cheon DS, Chae C. Distribution of porcine reproductive and respiratory syndrome virus in stillborn and liveborn piglets from experimentally infected sows. J Comp Pathol. 2001;124(4):231\u20137.","journal-title":"J Comp Pathol"},{"key":"2883_CR30","first-page":"1","volume":"14","author":"M Amadori","year":"2014","unstructured":"Amadori M, Razzuoli E. Immune control of PRRS: lessons to be learned and possible ways forward. Front Vet Sci. 2014;14:1.","journal-title":"Front Vet Sci"},{"key":"2883_CR31","doi-asserted-by":"publisher","first-page":"42","DOI":"10.3389\/fcell.2015.00042","volume":"3","author":"MJ Sch\u00f6nenberger","year":"2015","unstructured":"Sch\u00f6nenberger MJ. Hypoxia signaling pathways: modulators of oxygen-related organelles. Front Cell Dev Biol. 2015;3:42.","journal-title":"Front Cell Dev Biol"},{"issue":"6","key":"2883_CR32","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1038\/s12276-019-0235-1","volume":"51","author":"JW Lee","year":"2019","unstructured":"Lee JW, Ko J, Ju C, Eltzschig HK. Hypoxia signaling in human diseases and therapeutic targets. Exp Mol Med. 2019;51(6):68.","journal-title":"Exp Mol Med"},{"issue":"6525","key":"2883_CR33","doi-asserted-by":"publisher","first-page":"811","DOI":"10.1038\/374811a0","volume":"374","author":"S Shimizu","year":"1995","unstructured":"Shimizu S, Eguchi Y, Kosaka H, Kamiike W, Matsuda H, Tsujimoto Y. Prevention of hypoxia-induced cell death by Bcl-2 and Bcl-xL. Nature. 1995;374(6525):811\u20133.","journal-title":"Nature."},{"issue":"10","key":"2883_CR34","doi-asserted-by":"publisher","first-page":"1279","DOI":"10.1016\/j.freeradbiomed.2004.02.071","volume":"36","author":"P Goyal","year":"2004","unstructured":"Goyal P, Weissmann N, Grimminger F, Hegel C, Bader L, Rose F, et al. Upregulation of NAD(P)H oxidase 1 in hypoxia activates hypoxia-inducible factor 1 via increase in reactive oxygen species. Free Radic Biol Med. 2004;36(10):1279\u201388.","journal-title":"Free Radic Biol Med"},{"issue":"7","key":"2883_CR35","doi-asserted-by":"publisher","first-page":"829","DOI":"10.1093\/eurheartj\/ehr304","volume":"33","author":"U Forstermann","year":"2012","unstructured":"Forstermann U, Sessa WC. Nitric oxide synthases: regulation and function. Eur Heart J. 2012;33(7):829\u201337.","journal-title":"Eur Heart J"},{"issue":"451\u20134","key":"2883_CR36","doi-asserted-by":"publisher","first-page":"1467","DOI":"10.1152\/ajpheart.00682.2001","volume":"282","author":"LP Hale","year":"2002","unstructured":"Hale LP, Braun RD, Gwinn WM, Greer PK, Dewhirst MW. Hypoxia in the thymus: Role of oxygen tension in thymocyte survival. Am J Physiol Heart Circ Physiol. 2002;282(451\u20134):1467\u201377.","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"2883_CR37","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fimmu.2011.00027","volume":"2","author":"A Ohta","year":"2011","unstructured":"Ohta A, Diwanji R, Kini R, Subramanian M, Ohta A, Sitkovsky M. In vivo T cell activation in lymphoid tissues is inhibited in the oxygen-poor microenvironment. Front Immunol. 2011;2:1\u201310.","journal-title":"Front Immunol"},{"issue":"7","key":"2883_CR38","doi-asserted-by":"publisher","first-page":"e1002513","DOI":"10.1371\/journal.pbio.1002513","volume":"14","author":"LA Richardson","year":"2016","unstructured":"Richardson LA. Understanding disease tolerance and resilience. PLoS Biol. 2016;14(7):e1002513.","journal-title":"PLoS Biol"},{"key":"2883_CR39","first-page":"7","volume":"11","author":"CM Malgarin","year":"2020","unstructured":"Malgarin CM, MacPhee DJ, Harding JCS. Fetal metabolomic alterations following porcine reproductive and respiratory syndrome virus infection. Front Mol Biosci. 2020;11:7.","journal-title":"Front Mol Biosci"},{"issue":"3\u20134","key":"2883_CR40","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1016\/j.vetmic.2015.04.002","volume":"177","author":"Q Zhang","year":"2015","unstructured":"Zhang Q, Yoo D. PRRS virus receptors and their role for pathogenesis. Vet Microbiol. 2015;177(3\u20134):229\u201341.","journal-title":"Vet Microbiol"},{"issue":"3","key":"2883_CR41","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1016\/j.tjem.2018.08.001","volume":"18","author":"H Akoglu","year":"2018","unstructured":"Akoglu H. User\u2019s guide to correlation coefficients. Turkish J Emerg Med. 2018;18(3):91\u20133.","journal-title":"Turkish J Emerg Med"},{"issue":"8","key":"2883_CR42","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. Potential for a localized immune response by the ruminal epithelium in nonpregnant heifers following a short-term subacute ruminal acidosis challenge. J Dairy Sci. 2019;102(8):7556\u201369.","journal-title":"J Dairy Sci"},{"key":"2883_CR43","volume-title":"R: a language and environment for statistical computing. [internet]","author":"RC Team","year":"2020","unstructured":"Team RC. R: a language and environment for statistical computing. [internet]. Vienna: R Foundation for Statistical Computing; 2020."},{"key":"2883_CR44","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. ggplot2: Elegant Graphics for Data Analysis: Springer-Verlag New York; 2016."}],"container-title":["BMC Veterinary Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12917-021-02883-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12917-021-02883-0\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12917-021-02883-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,30]],"date-time":"2024-08-30T02:23:02Z","timestamp":1724984582000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcvetres.biomedcentral.com\/articles\/10.1186\/s12917-021-02883-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,1]]},"references-count":44,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["2883"],"URL":"https:\/\/doi.org\/10.1186\/s12917-021-02883-0","relation":{},"ISSN":["1746-6148"],"issn-type":[{"value":"1746-6148","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,1]]},"assertion":[{"value":"26 November 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 April 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 May 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This study was approved by the University of Saskatchewan Animal Research Ethics Board and adhered to the Canadian Council on Animal Care guidelines for humane animal use (Protocols 20110102 and 20160023). The infected pregnant gilts were closely monitored for clinical signs and a human intervention point checklist was established to monitor the gilts for critical conditions post-inoculation. It was not feasible to monitor fetal conditions after the viral inoculation, but fetal compromise death was expected to occur at the later time points. Gilts were euthanized with intravenous sodium pentobarbital overdose followed by cranial captive bolt and exsanguination. Fetuses were euthanized as humanely as possible given that pentobarbital sodium crosses the MFI rapidly and enters fetal circulation prior to the onset of hypoxia and asphyxia.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no conflicts of interest with respect to the research, authorship and\/or publication of this article.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"182"}}