{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:29:38Z","timestamp":1787027378640,"version":"build-2736575974"},"reference-count":34,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,10,14]],"date-time":"2021-10-14T00:00:00Z","timestamp":1634169600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Vet. Sci."],"abstract":"<jats:p>\n                    Interferon tau (IFNT), a pregnancy recognition signal in ruminants, promotes the establishment of embryo implantation by inducing the expression of interferon-stimulated genes (ISGs) via the Janus kinase\/signal transducer and activator of transcription (JAK\/STAT) signaling pathway. However, the precise regulatory mechanism of IFNT in goat embryo implantation remains largely unknown. In this study, we performed RNA sequencing of goat endometrial epithelial cells (gEECs) with or without 20 ng\/mL IFNT treatment. Differential comparison showed that there were 442 upregulated differentially expressed genes (DEGs) and 510 downregulated DEGs. Bioinformatic analyses revealed that DEGs were significantly enriched in immune-related functions or pathways. The qRT-PCR validation results showed that the expression levels of STAT family members (STAT1, STAT2, and STAT3) were significantly upregulated in gEECs after IFNT treatment, which is in agreement with the RNA-seq data. Meanwhile, the protein levels of p-STAT1 and p-STAT3 increased significantly in gEECs after 6 and 24 h of IFNT treatment, respectively. Further\n                    <jats:italic>in vivo<\/jats:italic>\n                    experiments also confirmed that both mRNA and protein phosphorylation levels of STAT1 and STAT3 in the uterus on day 18 of pregnancy (P18) were significantly increased compared to those on day 5 (P5) and day 15 of pregnancy (P15). On P5, STAT1 and STAT3 proteins were primarily located in the uterine luminal epithelium (LE) and glandular epithelium (GE), and were also detected in the stromal cells. The intense immunostaining of STAT1 and STAT3 proteins were decreased on P15 and then increased on P18, especially in the superficial GE and subepithelial stromal cells. Moreover, p-STAT1 and p-STAT3 were highly expressed in the deep GE on P18. Collectively, these results highlight the role of IFNT in regulating endometrial receptivity in gEECs and uncover the temporal and spatial changes in the expression of STAT1\/3 during embryo implantation in the goat endometrium.\n                  <\/jats:p>","DOI":"10.3389\/fvets.2021.757759","type":"journal-article","created":{"date-parts":[[2021,10,14]],"date-time":"2021-10-14T00:52:40Z","timestamp":1634172760000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":22,"title":["Transcriptomic Analysis of STAT1\/3 in the Goat Endometrium During Embryo Implantation"],"prefix":"10.3389","volume":"8","author":[{"given":"Haokun","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caixia","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zuhui","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunmei","family":"Shang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruixue","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aihua","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaping","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengfei","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,10,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1016\/j.theriogenology.2020.01.069","article-title":"Interferon tau: Influences on growth and development of the conceptus","volume":"150","author":"Bazer","year":"2020","journal-title":"Theriogenology."},{"key":"B2","doi-asserted-by":"publisher","first-page":"e3000046","DOI":"10.1371\/journal.pbio.3000046","article-title":"Fine-tuned adaptation of embryo-endometrium pairs at implantation revealed by transcriptome analyses in Bos taurus","volume":"17","author":"Biase","year":"2019","journal-title":"PLoS Biol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"106251","DOI":"10.1016\/j.anireprosci.2019.106251","article-title":"Pregnancy loss in beef cattle: a meta-analysis","volume":"212","author":"Reese","year":"2020","journal-title":"Anim Reprod Sci."},{"key":"B4","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1016\/j.theriogenology.2016.04.037","article-title":"Pivotal periods for pregnancy loss during the first trimester of gestation in lactating dairy cows","volume":"86","author":"Wiltbank","year":"2016","journal-title":"Theriogenology."},{"key":"B5","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1152\/physiolgenomics.00047.2010","article-title":"Bovine pretransfer endometrium and embryo transcriptome fingerprints as predictors of pregnancy success after embryo transfer","volume":"42","author":"Salilew-Wondim","year":"2010","journal-title":"Physiol Genomics."},{"key":"B6","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1095\/biolreprod.111.091587","article-title":"Transcriptome changes at the initiation of elongation in the bovine conceptus","volume":"85","author":"Clemente","year":"2011","journal-title":"Biol Reprod."},{"key":"B7","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1016\/j.theriogenology.2017.01.021","article-title":"The effect of lysophosphatidic acid together with interferon tau on the global transcriptomic profile in bovine endometrial cells","volume":"92","author":"Boruszewska","year":"2017","journal-title":"Theriogenology."},{"key":"B8","doi-asserted-by":"publisher","first-page":"16981","DOI":"10.1038\/s41598-020-72988-3","article-title":"Machine learning approach to integrated endometrial transcriptomic datasets reveals biomarkers predicting uterine receptivity in cattle at seven days after estrous","volume":"10","author":"Rabaglino","year":"2020","journal-title":"Sci Rep."},{"key":"B9","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1016\/j.cytogfr.2007.06.010","article-title":"Interferon-tau, a Type 1 interferon involved in maternal recognition of pregnancy","volume":"18","author":"Roberts","year":"2007","journal-title":"Cytokine Growth Factor Rev."},{"key":"B10","doi-asserted-by":"publisher","first-page":"1627","DOI":"10.2527\/jas.2012-5845","article-title":"Physiology and endocrinology symposium: biological role of interferon tau in endometrial function and conceptus elongation","volume":"91","author":"Dorniak","year":"2013","journal-title":"J Anim Sci."},{"key":"B11","doi-asserted-by":"publisher","first-page":"1312","DOI":"10.1128\/MCB.15.3.1312","article-title":"Role of STAT2 in the alpha interferon signaling pathway","volume":"15","author":"Leung","year":"1995","journal-title":"Mol Cell Biol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"20775","DOI":"10.1074\/jbc.270.35.20775","article-title":"Phosphorylation, and activation of the DNA binding activity of purified Stat1 by the Janus protein-tyrosine kinases and the epidermal growth factor receptor","volume":"270","author":"Quelle","year":"1995","journal-title":"J Biol Chem."},{"key":"B13","doi-asserted-by":"publisher","first-page":"8521","DOI":"10.1073\/pnas.85.22.8521","article-title":"Two interferon-induced nuclear factors bind a single promoter element in interferon-stimulated genes","volume":"85","author":"Kessler","year":"1988","journal-title":"Proc Natl Acad Sci USA."},{"key":"B14","doi-asserted-by":"publisher","first-page":"5605","DOI":"10.1002\/j.1460-2075.1994.tb06898.x","article-title":"Activation of JAK kinases and STAT proteins by interleukin-2 and interferon alpha, but not the T cell antigen receptor, in human T lymphocytes","volume":"13","author":"Beadling","year":"1994","journal-title":"Embo J."},{"key":"B15","doi-asserted-by":"publisher","first-page":"18967","DOI":"10.1074\/jbc.M314037200","article-title":"Structural requirements for signal transducer and activator of transcription 3 binding to phosphotyrosine ligands containing the YXXQ motif","volume":"279","author":"Shao","year":"2004","journal-title":"J Biol Chem."},{"key":"B16","doi-asserted-by":"publisher","first-page":"4134","DOI":"10.1074\/jbc.271.8.4134","article-title":"Preassociation of STAT1 with STAT2 and STAT3 in separate signalling complexes prior to cytokine stimulation","volume":"271","author":"Stancato","year":"1996","journal-title":"J Biol Chem."},{"key":"B17","doi-asserted-by":"publisher","first-page":"1038","DOI":"10.1095\/biolreprod65.4.1038","article-title":"Interferon regulatory factor-two restricts expression of interferon-stimulated genes to the endometrial stroma and glandular epithelium of the ovine uterus","volume":"65","author":"Choi","year":"2001","journal-title":"Biol Reprod."},{"key":"B18","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1071\/RD14034","article-title":"Analysis of STAT1 expression and biological activity reveals interferon-tau-dependent STAT1-regulated SOCS genes in the bovine endometrium","volume":"28","author":"Vitorino","year":"2016","journal-title":"Reprod Fertil Dev."},{"key":"B19","doi-asserted-by":"publisher","first-page":"15523","DOI":"10.1038\/s41598-020-72640-0","article-title":"Differential roles of uterine epithelial and stromal STAT3 coordinate uterine receptivity and embryo attachment","volume":"10","author":"Hiraoka","year":"2020","journal-title":"Sci Rep."},{"key":"B20","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1530\/rep.1.00053","article-title":"Signal transducer and activator of transcription 3 (Stat3) expression and activation in rat uterus during early pregnancy","volume":"128","author":"Teng","year":"2004","journal-title":"Reproduction."},{"key":"B21","doi-asserted-by":"publisher","first-page":"2738","DOI":"10.3923\/javaa.2010.2738.2747","article-title":"Establishment and characteristics of immortal goat endometrial epithelial cells and stromal cells with hTERT","volume":"9","author":"Zhang","year":"2010","journal-title":"J Anim Vet Adv."},{"key":"B22","doi-asserted-by":"publisher","first-page":"669","DOI":"10.1093\/biolre\/ioaa226","article-title":"Conceptus-induced, interferon tau-dependent gene expression in bovine endometrial epithelial and stromal cells\u2020","volume":"104","author":"Chaney","year":"2021","journal-title":"Biol Reprod."},{"key":"B23","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1016\/j.gene.2017.08.026","article-title":"The developmental transcriptome landscape of receptive endometrium during embryo implantation in dairy goats","volume":"633","author":"Zhang","year":"2017","journal-title":"Gene."},{"key":"B24","doi-asserted-by":"publisher","first-page":"383","DOI":"10.95\/biolreprod.105.046656","article-title":"Identification of endometrial genes regulated by early pregnancy, progesterone, and interferon tau in the ovine uterus","volume":"74","author":"Gray","year":"2006","journal-title":"Biol Reprod."},{"key":"B25","doi-asserted-by":"publisher","first-page":"e202002175","DOI":"10.1083\/jcb.202002175","article-title":"Interferon-stimulated gene 15 accelerates replication fork progression inducing chromosomal breakage","volume":"219","author":"Raso","year":"2020","journal-title":"J Cell Biol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"164","DOI":"10.3390\/vaccines9020164","article-title":"Proteomic analysis of ISGylation in immortalized porcine alveolar macrophage cell lines induced by type I interferon","volume":"9","author":"Zhu","year":"2021","journal-title":"Vaccines."},{"key":"B27","doi-asserted-by":"publisher","first-page":"e0122874","DOI":"10.1371\/journal.pone.0122874","article-title":"The transcriptome signature of the receptive bovine uterus determined at early gestation","volume":"10","author":"Binelli","year":"2015","journal-title":"PLoS ONE."},{"key":"B28","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1186\/s12967-021-02837-y","article-title":"The role of transcriptomic biomarkers of endometrial receptivity in personalized embryo transfer for patients with repeated implantation failure","volume":"19","author":"He","year":"2021","journal-title":"J Transl Med."},{"key":"B29","doi-asserted-by":"publisher","first-page":"654","DOI":"10.1095\/biolreprod","article-title":"Bovine interferon-tau stimulates the Janus kinase-signal transducer and activator of transcription pathway in bovine endometrial epithelial cells","volume":"64","author":"Binelli","year":"2001","journal-title":"Biol Reprod."},{"key":"B30","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1210\/endo.142.1.7891","article-title":"Interferon-tau activates multiple signal transducer and activator of transcription proteins and has complex effects on interferon-responsive gene transcription in ovine endometrial epithelial cells","volume":"142","author":"Stewart","year":"2001","journal-title":"Endocrinology."},{"key":"B31","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1093\/biolre\/ioy047","article-title":"Mechanisms for the establishment and maintenance of pregnancy: synergies from scientific collaborations","volume":"99","author":"Bazer","year":"2018","journal-title":"Biol Reprod."},{"key":"B32","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1530\/REP-10-0348","article-title":"Pregnancy, and interferon tau regulate DDX58 and PLSCR1 in the ovine uterus during the peri-implantation period","volume":"141","author":"Song","year":"2011","journal-title":"Reproduction."},{"key":"B33","doi-asserted-by":"publisher","first-page":"675","DOI":"10.1210\/en.2004-1224","article-title":"Interferon stimulated gene 15 conjugates to endometrial cytosolic proteins and is expressed at the uterine-placental interface throughout pregnancy in sheep","volume":"146","author":"Joyce","year":"2005","journal-title":"Endocrinology."},{"key":"B34","doi-asserted-by":"publisher","first-page":"9373","DOI":"10.1073\/pnas.0903487106","article-title":"Unphosphorylated STAT1 prolongs the expression of interferon-induced immune regulatory genes","volume":"106","author":"Cheon","year":"2009","journal-title":"Proc Natl Acad Sci USA."}],"container-title":["Frontiers in Veterinary Science"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fvets.2021.757759\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,10,14]],"date-time":"2021-10-14T00:52:42Z","timestamp":1634172762000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fvets.2021.757759\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,14]]},"references-count":34,"alternative-id":["10.3389\/fvets.2021.757759"],"URL":"https:\/\/doi.org\/10.3389\/fvets.2021.757759","relation":{},"ISSN":["2297-1769"],"issn-type":[{"value":"2297-1769","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,14]]},"article-number":"757759"}}