{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T10:54:14Z","timestamp":1790247254275,"version":"4.1.0"},"reference-count":59,"publisher":"Oxford University Press (OUP)","issue":"Supplement_6","license":[{"start":{"date-parts":[[2021,7,22]],"date-time":"2021-07-22T00:00:00Z","timestamp":1626912000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100007165","name":"University of Missouri","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007165","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["3R01HD094937"],"award-info":[{"award-number":["3R01HD094937"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1R21AI145071"],"award-info":[{"award-number":["1R21AI145071"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["3R01HD100022-02S2"],"award-info":[{"award-number":["3R01HD100022-02S2"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1R01HD100022"],"award-info":[{"award-number":["1R01HD100022"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,12,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>SARS-CoV-2 infection in term placenta is rare. However, growing evidence suggests that susceptibility of the human placenta to infection may vary by gestational age and pathogen. For several viral infections, susceptibility appears to be greatest during early gestation. Peri-implantation placental infections that result in pre-clinical pregnancy loss would typically go undetected. Little is known about the effects of SARS-CoV-2 on the peri-implantation human placenta since this time in pregnancy can only be modeled in vitro.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We used a human embryonic stem cell (hESC)-derived model of peri-implantation placental development to assess patterns of ACE2 and TMPRSS2 transcription and protein expression in primitive trophoblast. We then infected the same trophoblast cell model with a clinical isolate of SARS-CoV-2 and documented infection dynamics.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>ACE2 and TMPRSS2 were transcribed and translated in hESC-derived trophoblast, with preferential expression in syncytialized cells. These same cells supported replicative and persistent infection by SARS-CoV-2, while non-syncytialized trophoblast cells in the same cultures did not.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Co-expression of ACE2 and TMPRSS2 in hESC-derived trophoblast and the robust and replicative infection limited to syncytiotrophoblast equivalents support the hypothesis that increased viral susceptibility may be a defining characteristic of primitive trophoblast.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/infdis\/jiab309","type":"journal-article","created":{"date-parts":[[2021,6,8]],"date-time":"2021-06-08T19:12:11Z","timestamp":1623179531000},"page":"S660-S669","source":"Crossref","is-referenced-by-count":15,"title":["Is SARS-CoV-2 Infection a Risk Factor for Early Pregnancy Loss? ACE2 and TMPRSS2 Coexpression and Persistent Replicative Infection in Primitive Trophoblast"],"prefix":"10.1093","volume":"224","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6991-9766","authenticated-orcid":false,"given":"Jie","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Obstetrics, Gynecology, and Women\u2019s Health, University of Missouri School of Medicine, Columbia, Missouri, USA"},{"name":"Christopher S Bond Life Sciences Center, University of Missouri, Columbia, Missouri, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sehee","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Gynecology, and Women\u2019s Health, University of Missouri School of Medicine, Columbia, Missouri, USA"},{"name":"Christopher S Bond Life Sciences Center, University of Missouri, Columbia, Missouri, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heidi","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, School of Medicine, University of Missouri, Columbia, Missouri, USA"},{"name":"Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Missouri, Columbia, Missouri, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jialin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, School of Medicine, University of Missouri, Columbia, Missouri, USA"},{"name":"Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Missouri, Columbia, Missouri, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuchen","family":"Tian","sequence":"additional","affiliation":[{"name":"Christopher S Bond Life Sciences Center, University of Missouri, Columbia, Missouri, USA"},{"name":"Division of Animal Sciences, Bond Life Sciences Center, University of Missouri, Columbia, Missouri, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea G","family":"Edlow","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA"},{"name":"Vincent Center for Reproductive Biology, Massachusetts General Hospital, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshihiko","family":"Ezashi","sequence":"additional","affiliation":[{"name":"Christopher S Bond Life Sciences Center, University of Missouri, Columbia, Missouri, USA"},{"name":"Division of Animal Sciences, Bond Life Sciences Center, University of Missouri, Columbia, Missouri, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R Michael","family":"Roberts","sequence":"additional","affiliation":[{"name":"Christopher S Bond Life Sciences Center, University of Missouri, Columbia, Missouri, USA"},{"name":"Division of Animal Sciences, Bond Life Sciences Center, University of Missouri, Columbia, Missouri, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjun","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, School of Medicine, University of Missouri, Columbia, Missouri, USA"},{"name":"Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Missouri, Columbia, Missouri, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danny J","family":"Schust","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Gynecology, and Women\u2019s Health, University of Missouri School of Medicine, Columbia, Missouri, 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