{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T10:06:56Z","timestamp":1753870016968,"version":"3.41.2"},"reference-count":43,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,1,27]],"date-time":"2025-01-27T00:00:00Z","timestamp":1737936000000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,1,27]],"date-time":"2025-01-27T00:00:00Z","timestamp":1737936000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000923","name":"Australian Research Council","doi-asserted-by":"publisher","award":["DE220100121","FT220100557"],"award-info":[{"award-number":["DE220100121","FT220100557"]}],"id":[{"id":"10.13039\/501100000923","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Proteomics Clinical Apps"],"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Purpose<\/jats:title><jats:p>Embryo\u2010maternal signaling during the establishment of pregnancy in horses remains one of the biggest mysteries in large animal physiology. Early pregnancy loss represents a major source of economic loss to the breeding industry. This study aimed to investigate the systemic changes associated with early pregnancy by mapping the proteome of blood plasma at 14 days in pregnant and non\u2010pregnant mares.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Design<\/jats:title><jats:p>Plasma proteomes were analysed\u00a0in commercially bred pregnant (<jats:italic>n<\/jats:italic>\u00a0=\u00a017) and non\u2010pregnant (<jats:italic>n<\/jats:italic>\u00a0=\u00a017) Thoroughbred mares at 14 days after ovulation, using high\u2010resolution mass spectrometry. Day 14 histotroph and yolk sac fluid were also profiled and datasets were integrated through pathway analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We identified 229 total protein IDs, with 12 increased and 10 decreased significantly in pregnant versus non\u2010pregnant plasma. To gain functional insight, these data were aligned with proteomes of 14\u2010day pregnant mare uterine fluid (<jats:italic>n<\/jats:italic>\u00a0=\u00a04; 1358 IDs) and conceptus fluid (soluble proteins within the yolk sac fluid; <jats:italic>n<\/jats:italic>\u00a0=\u00a04; 1152 IDs), and further interrogated using gene ontology databases and pathway analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Clinical Relevance<\/jats:title><jats:p>These analyses identified consistent systemic changes in the mare's proteome that indicate a profound and specific immune response to early pregnancy, which appears to precede the systemic endocrine response to pregnancy. Integrated pathway analysis suggests that embryo\u2010maternal interactions in early pregnancy may mimic elements of the virus\u2010host interaction to modulate the maternal immune response. Transthyretin (TTR) and uteroglobin (SCGB1A1) were respectively down\u2010 and upregulated in plasma while also present in uterine fluid, and are proposed to be key proteins in early pregnancy establishment. These findings contribute significantly to our knowledge of early pregnancy in the mare and identify potential new avenues for developing clinical approaches to reduce early embryo loss.<\/jats:p><\/jats:sec>","DOI":"10.1002\/prca.202400095","type":"journal-article","created":{"date-parts":[[2025,1,27]],"date-time":"2025-01-27T11:25:34Z","timestamp":1737977134000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Systemic Changes in Early Pregnancy in the Mare: An Integrated Proteomic Analysis of Blood Plasma, Histotroph, and Yolk Sac Fluid at Day 14 Post\u2010Ovulation"],"prefix":"10.1002","volume":"19","author":[{"given":"Tharangani R. W.","family":"Perera","sequence":"first","affiliation":[{"name":"Priority Research Centre for Reproductive Science School of Environmental and Life Sciences College of Engineering Science and Environment The University of Newcastle  Callaghan New South Wales Australia"},{"name":"Infertility and Reproduction Research Program Hunter Medical Research Institute  New Lambton Heights New South Wales Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marta","family":"de Ruijter\u2010Villani","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences Utrecht University  Utrecht The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zamira","family":"Gibb","sequence":"additional","affiliation":[{"name":"Priority Research Centre for Reproductive Science School of Environmental and Life Sciences College of Engineering Science and Environment The University of Newcastle  Callaghan New South Wales Australia"},{"name":"Infertility and Reproduction Research Program Hunter Medical Research Institute  New Lambton Heights New South Wales Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2745-8188","authenticated-orcid":false,"given":"Brett","family":"Nixon","sequence":"additional","affiliation":[{"name":"Priority Research Centre for Reproductive Science School of Environmental and Life Sciences College of Engineering Science and Environment The University of Newcastle  Callaghan New South Wales Australia"},{"name":"Infertility and Reproduction Research Program Hunter Medical Research Institute  New Lambton Heights New South Wales Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alecia","family":"Sheridan","sequence":"additional","affiliation":[{"name":"Priority Research Centre for Reproductive Science School of Environmental and Life Sciences College of Engineering Science and Environment The University of Newcastle  Callaghan New South Wales Australia"},{"name":"Infertility and Reproduction Research Program Hunter Medical Research Institute  New Lambton Heights New South Wales Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tom A. E.","family":"Stout","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences Utrecht University  Utrecht The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7371-5400","authenticated-orcid":false,"given":"Aleona","family":"Swegen","sequence":"additional","affiliation":[{"name":"Priority Research Centre for Reproductive Science School of Environmental and Life Sciences College of Engineering Science and Environment The University of Newcastle  Callaghan New South Wales Australia"},{"name":"Infertility and Reproduction Research Program Hunter Medical Research Institute  New Lambton Heights New South Wales Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1804-1826","authenticated-orcid":false,"given":"David A.","family":"Skerrett\u2010Byrne","sequence":"additional","affiliation":[{"name":"Priority Research Centre for Reproductive Science School of 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