{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T14:56:20Z","timestamp":1791644180507,"version":"4.3.4"},"reference-count":63,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2020,11,3]],"date-time":"2020-11-03T00:00:00Z","timestamp":1604361600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"New Mexico Agricultural Experiment Station"},{"name":"Cowboys for Cancer Research Award"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,2,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Early pregnancy features complex signaling between fetal trophoblast cells and maternal endometrium directing major peri-implantation events including localized inflammation and remodeling to establish proper placental development. Proinflammatory mediators are important for conceptus attachment, but a more precise understanding of molecular pathways regulating this process is needed to understand how the endometrium becomes receptive to implantation. Both chemokine ligand 12 (CXCL12) and its receptor CXCR4 are expressed by fetal and maternal tissues. We identified this pair as a critical driver of placental angiogenesis, but their additional importance to inflammation and trophoblast cell survival, proliferation, and invasion imply a role in syncytia formation at the fetal\u2013maternal microenvironment. We hypothesized that CXCL12 encourages both endometrial inflammation and conceptus attachment during implantation. We employed separate ovine studies to (1) characterize endometrial inflammation during early gestation in the ewe, and (2) establish functional implications of CXCL12 at the fetal\u2013maternal interface through targeted intrauterine infusion of the CXCR4 inhibitor AMD3100. Endometrial tissues were evaluated for inflammatory mediators, intracellular signaling events, endometrial modifications, and trophoblast syncytialization using western blotting and immunohistochemistry. Endometrial tissue from ewes receiving CXCR4 inhibitor demonstrated dysregulated inflammation and reduced AKT and NFKB, paired with elevated autophagic activity compared to control. Immunohistochemical observation revealed an impairment in endometrial surface remodeling and diminished trophoblast syncytialization following localized CXCR4 inhibition. These data suggest CXCL12\u2013CXCR4 regulates endometrial inflammation and remodeling for embryonic implantation, and provide insight regarding mechanisms that, when dysregulated, lead to pregnancy pathologies such as intrauterine growth restriction and preeclampsia.<\/jats:p>","DOI":"10.1093\/biolre\/ioaa203","type":"journal-article","created":{"date-parts":[[2020,11,3]],"date-time":"2020-11-03T13:01:08Z","timestamp":1604408468000},"page":"468-478","source":"Crossref","is-referenced-by-count":13,"title":["CXCR4 signaling at the fetal\u2013maternal interface may drive inflammation and syncytia formation during ovine pregnancy\u2020"],"prefix":"10.1093","volume":"104","author":[{"given":"Stacia Z","family":"McIntosh","sequence":"first","affiliation":[{"name":"Department of Animal and Range Sciences, New Mexico State University, Las Cruces, NM, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marlie M","family":"Maestas","sequence":"additional","affiliation":[{"name":"Department of Animal and Range Sciences, New Mexico State University, Las Cruces, NM, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordyn R","family":"Dobson","sequence":"additional","affiliation":[{"name":"Department of Animal and Range Sciences, New Mexico State University, Las Cruces, NM, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelsey E","family":"Quinn","sequence":"additional","affiliation":[{"name":"Department of Animal and Range Sciences, New Mexico State University, Las Cruces, NM, USA"},{"name":"Department of Cell Biology and Physiology, University of North Carolina, Chapel Hill, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheyenne L","family":"Runyan","sequence":"additional","affiliation":[{"name":"Department of Animal and Range Sciences, New Mexico State University, Las Cruces, NM, USA"},{"name":"Department of Animal Science & Veterinary Technology, Tarleton State University, Stephenville, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan L","family":"Ashley","sequence":"additional","affiliation":[{"name":"Department of Animal and Range Sciences, New Mexico State University, Las Cruces, NM, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,11,3]]},"reference":[{"key":"2021021110455620200_ref1","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1111\/aji.12450","article-title":"The microenvironment of human implantation: Determinant of reproductive success","volume":"75","author":"Salamonsen","year":"2016","journal-title":"Am J Reprod Immunol"},{"key":"2021021110455620200_ref2","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1042\/CS20150702","article-title":"The role of inflammation in the pathology of preeclampsia","volume":"130","author":"Harmon","year":"2016","journal-title":"Clin Sci"},{"key":"2021021110455620200_ref3","first-page":"1122","article-title":"Hypertension in pregnancy. 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