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This effect is particularly profound following fetal infection, whereby the ability to decrease circulating triiodothyronine is associated with resilience following late\u2010gestation infection. We have previously shown that the thyroidal response to fetal infection is associated with peripheral changes in deiodinase activity, but the role of the central regulatory axis has not been established. To assess this, we characterized the impact of fetal PRRSV infection on gene expression within the hypothalamic\u2013pituitary\u2010thyroid (HPT) and \u2010adrenal (HPA) axes and further assessed the impact of fetal genotype at a previously identified single nucleotide polymorphism found to contribute to PRRSV\u2010resilience. In this study, fetal infection and the corresponding NTIS\u2010like state were associated with modulations in both the HPT and HPA axes, with the most marked effects observed within the thyroid and adrenals, respectively. In the HPT axis, our results indicate altered thyroid hormone metabolism and signaling, with dysregulation of key thyroid hormone receptor, deiodinase, and transporter genes. Similarly, in the HPA axis, the observed transcriptional dysregulations indicate alterations in both steroidogenesis and catecholamine production, with increases in circulating cortisol also indicating a disruption within this system. The results were found to be partially dependent on fetal genotype, collectively providing insights into not only the impact of fetal infection on these critical endocrine systems, but the impact of genotype on the endocrine response to infection.<\/jats:p>","DOI":"10.1002\/cph4.70112","type":"journal-article","created":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T03:46:33Z","timestamp":1770695193000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Hypothalamic\u2013Pituitary\u2013Thyroid and Adrenal Axis Modulation in Response to Fetal Porcine Reproductive and Respiratory Virus Infection"],"prefix":"10.1002","volume":"16","author":[{"given":"Alyssa A.","family":"Smith","sequence":"first","affiliation":[{"name":"Department of Animal Sciences Purdue University  West Lafayette Indiana USA"},{"name":"Department of Animal and Food Sciences University of Kentucky  Lexington Kentucky USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Glenn","family":"Hamonic","sequence":"additional","affiliation":[{"name":"Department of Large Animal Clinical Sciences, Western College of Veterinary Medicine University of Saskatchewan  Saskatoon Saskatchewan Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graham S.","family":"Plastow","sequence":"additional","affiliation":[{"name":"Department of Agricultural, Food and Nutritional Science University of Alberta  Edmonton Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John C. 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