Is SARS-CoV-2 Infection a Risk Factor for Early Pregnancy Loss? ACE2 and TMPRSS2 Coexpression and Persistent Replicative Infection in Primitive Trophoblast

BACKGROUND: 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...

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Autores principales: Zhou, Jie, Choi, Sehee, Liu, Heidi, Zhang, Jialin, Tian, Yuchen, Edlow, Andrea G, Ezashi, Toshihiko, Roberts, R Michael, Ma, Wenjun, Schust, Danny J
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8411376/
https://www.ncbi.nlm.nih.gov/pubmed/34293134
http://dx.doi.org/10.1093/infdis/jiab309
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author Zhou, Jie
Choi, Sehee
Liu, Heidi
Zhang, Jialin
Tian, Yuchen
Edlow, Andrea G
Ezashi, Toshihiko
Roberts, R Michael
Ma, Wenjun
Schust, Danny J
author_facet Zhou, Jie
Choi, Sehee
Liu, Heidi
Zhang, Jialin
Tian, Yuchen
Edlow, Andrea G
Ezashi, Toshihiko
Roberts, R Michael
Ma, Wenjun
Schust, Danny J
author_sort Zhou, Jie
collection PubMed
description BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
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spelling pubmed-84113762021-09-10 Is SARS-CoV-2 Infection a Risk Factor for Early Pregnancy Loss? ACE2 and TMPRSS2 Coexpression and Persistent Replicative Infection in Primitive Trophoblast Zhou, Jie Choi, Sehee Liu, Heidi Zhang, Jialin Tian, Yuchen Edlow, Andrea G Ezashi, Toshihiko Roberts, R Michael Ma, Wenjun Schust, Danny J J Infect Dis Supplement Articles BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. Oxford University Press 2021-07-22 /pmc/articles/PMC8411376/ /pubmed/34293134 http://dx.doi.org/10.1093/infdis/jiab309 Text en © The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com. https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_modelThis article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)
spellingShingle Supplement Articles
Zhou, Jie
Choi, Sehee
Liu, Heidi
Zhang, Jialin
Tian, Yuchen
Edlow, Andrea G
Ezashi, Toshihiko
Roberts, R Michael
Ma, Wenjun
Schust, Danny J
Is SARS-CoV-2 Infection a Risk Factor for Early Pregnancy Loss? ACE2 and TMPRSS2 Coexpression and Persistent Replicative Infection in Primitive Trophoblast
title Is SARS-CoV-2 Infection a Risk Factor for Early Pregnancy Loss? ACE2 and TMPRSS2 Coexpression and Persistent Replicative Infection in Primitive Trophoblast
title_full Is SARS-CoV-2 Infection a Risk Factor for Early Pregnancy Loss? ACE2 and TMPRSS2 Coexpression and Persistent Replicative Infection in Primitive Trophoblast
title_fullStr Is SARS-CoV-2 Infection a Risk Factor for Early Pregnancy Loss? ACE2 and TMPRSS2 Coexpression and Persistent Replicative Infection in Primitive Trophoblast
title_full_unstemmed Is SARS-CoV-2 Infection a Risk Factor for Early Pregnancy Loss? ACE2 and TMPRSS2 Coexpression and Persistent Replicative Infection in Primitive Trophoblast
title_short Is SARS-CoV-2 Infection a Risk Factor for Early Pregnancy Loss? ACE2 and TMPRSS2 Coexpression and Persistent Replicative Infection in Primitive Trophoblast
title_sort is sars-cov-2 infection a risk factor for early pregnancy loss? ace2 and tmprss2 coexpression and persistent replicative infection in primitive trophoblast
topic Supplement Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8411376/
https://www.ncbi.nlm.nih.gov/pubmed/34293134
http://dx.doi.org/10.1093/infdis/jiab309
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