{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T23:19:30Z","timestamp":1790637570832,"version":"4.1.0"},"reference-count":53,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2018,7,31]],"date-time":"2018-07-31T00:00:00Z","timestamp":1532995200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Department of Microbiology and Immunology at Chicago Medical School at RFUMS"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J Rep Immunol"],"published-print":{"date-parts":[[2018,10]]},"abstract":"<jats:sec><jats:title>Problem<\/jats:title><jats:p>Angiogenesis and vascular remodeling in secretory endometrium represent one of the crucial steps in pregnancy establishment, for which uterine NK (<jats:styled-content style=\"fixed-case\">uNK<\/jats:styled-content>) cells have an important role. Impairment of these steps may proceed to implantation and instigate initial pathology of recurrent pregnancy losses (RPL). In this study, we aim to investigate vascular development and density of <jats:styled-content style=\"fixed-case\">uNK<\/jats:styled-content> cells in secretory endometrium of women with RPL.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods of study<\/jats:title><jats:p>Mid\u2010secretory phase endometrial tissues from women with <jats:styled-content style=\"fixed-case\">RPL<\/jats:styled-content> (n\u00a0=\u00a015) and fertile controls (n\u00a0=\u00a07) were investigated. <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>56<jats:sup>+<\/jats:sup> and <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>16<jats:sup>+<\/jats:sup> <jats:styled-content style=\"fixed-case\">uNK<\/jats:styled-content> cells, <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>31<jats:sup>+<\/jats:sup> vascular endothelial cells and smooth muscle myosin (<jats:styled-content style=\"fixed-case\">SMM<\/jats:styled-content>)<jats:sup>+<\/jats:sup>. Vascular smooth muscle cells (<jats:styled-content style=\"fixed-case\">VSMC<\/jats:styled-content>) expressing <jats:styled-content style=\"fixed-case\">SMM<\/jats:styled-content> were investigated using immunohistochemistry and western blot. High\u2010throughput quantitative real\u2010time polymerase chain reaction (<jats:styled-content style=\"fixed-case\">qRT<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">PCR<\/jats:styled-content>) was used as well.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>56<jats:sup>+<\/jats:sup> <jats:styled-content style=\"fixed-case\">uNK<\/jats:styled-content> number was significantly higher in women with <jats:styled-content style=\"fixed-case\">RPL<\/jats:styled-content> compared to controls (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.0001). <jats:styled-content style=\"fixed-case\">uNK<\/jats:styled-content> cell density by immunohistochemistry was positively correlated with <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>56 <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> expression by <jats:styled-content style=\"fixed-case\">qRT<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">PCR<\/jats:styled-content> (<jats:italic>r<\/jats:italic><jats:sup>2<\/jats:sup>\u00a0=\u00a00.43, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.0137). The number of blood vessels represented by the expression of either <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>31 or <jats:styled-content style=\"fixed-case\">SMM<\/jats:styled-content> was higher in women with <jats:styled-content style=\"fixed-case\">RPL<\/jats:styled-content> as compared to controls (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05 and <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.0001, respectively), and correlated with the number of <jats:styled-content style=\"fixed-case\">uNK<\/jats:styled-content> cell (<jats:italic>r<\/jats:italic><jats:sup>2<\/jats:sup>\u00a0=\u00a00.18, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.04, and <jats:italic>r<\/jats:italic><jats:sup>2<\/jats:sup>\u00a0=\u00a00.65, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.0001, respectively). The wall thickness of spiral arteries was significantly higher in women with <jats:styled-content style=\"fixed-case\">RPL<\/jats:styled-content> as compared with that of controls (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.0027).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Increased <jats:styled-content style=\"fixed-case\">uNK<\/jats:styled-content> cells in mid\u2010secretory endometrium are associated with increased vascularization and defective vascular transformation of spiral arteries in women with <jats:styled-content style=\"fixed-case\">RPL<\/jats:styled-content>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/aji.13024","type":"journal-article","created":{"date-parts":[[2018,8,1]],"date-time":"2018-08-01T13:12:00Z","timestamp":1533129120000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":64,"title":["Dysregulated uterine natural killer cells and vascular remodeling in women with recurrent pregnancy losses"],"prefix":"10.1111","volume":"80","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4529-9328","authenticated-orcid":false,"given":"Haidy","family":"El\u2010Azzamy","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology Chicago Medical School at Rosalind Franklin University of Medicine and Science  North Chicago Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svetlana V.","family":"Dambaeva","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology Chicago Medical School at Rosalind Franklin University of Medicine and Science  North Chicago Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimantha","family":"Katukurundage","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology Chicago Medical School at Rosalind Franklin University of Medicine and Science  North Chicago Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria D.","family":"Salazar Garcia","sequence":"additional","affiliation":[{"name":"Reproductive Medicine and Immunology Department of Obstetrics and Gynecology Chicago Medical School at Rosalind Franklin University of Medicine and Science  North Chicago Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3643-4882","authenticated-orcid":false,"given":"Annie","family":"Skariah","sequence":"additional","affiliation":[{"name":"Reproductive Medicine and Immunology Department of Obstetrics and Gynecology Chicago Medical School at Rosalind Franklin University of Medicine and Science  North Chicago Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youssef","family":"Hussein","sequence":"additional","affiliation":[{"name":"Reproductive Medicine and Immunology Department of Obstetrics and Gynecology Chicago Medical School at Rosalind Franklin 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