A placental model of SARS-CoV-2 infection reveals ACE2-dependent susceptibility and differentiation impairment in syncytiotrophoblasts

J. Chen; J. A. Neil; J. P. Tan; R. Rudraraju; M. Mohenska; Y. B.Y. Sun; E. Walters; N. G. Bediaga; G. Sun; Y. Zhou; Y. Li; D. Drew; P. Pymm; W. H. Tham; F. J. Rossello; G. Nie; X. Liu; K. Subbarao; J. M. Polo

doi:10.1038/s41556-023-01182-0

A placental model of SARS-CoV-2 infection reveals ACE2-dependent susceptibility and differentiation impairment in syncytiotrophoblasts

J. Chen, J. A. Neil, J. P. Tan, R. Rudraraju, M. Mohenska, Y. B.Y. Sun, E. Walters, N. G. Bediaga, G. Sun, Y. Zhou, Y. Li, D. Drew, P. Pymm, W. H. Tham, F. J. Rossello, G. Nie, X. Liu, K. Subbarao^*, J. M. Polo^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

15 Citations (Scopus)

Abstract

SARS-CoV-2 infection causes COVID-19. Several clinical reports have linked COVID-19 during pregnancy to negative birth outcomes and placentitis. However, the pathophysiological mechanisms underpinning SARS-CoV-2 infection during placentation and early pregnancy are not clear. Here, to shed light on this, we used induced trophoblast stem cells to generate an in vitro early placenta infection model. We identified that syncytiotrophoblasts could be infected through angiotensin-converting enzyme 2 (ACE2). Using a co-culture model of vertical transmission, we confirmed the ability of the virus to infect syncytiotrophoblasts through a previous endometrial cell infection. We further demonstrated transcriptional changes in infected syncytiotrophoblasts that led to impairment of cellular processes, reduced secretion of HCG hormone and morphological changes vital for syncytiotrophoblast function. Furthermore, different antibody strategies and antiviral drugs restore these impairments. In summary, we have established a scalable and tractable platform to study early placental cell types and highlighted its use in studying strategies to protect the placenta.

Original language	English
Pages (from-to)	1223-1234
Number of pages	12
Journal	Nature Cell Biology
Volume	25
Issue number	8
DOIs	https://doi.org/10.1038/s41556-023-01182-0
Publication status	Published - 2023
Externally published	Yes

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Chen, J., Neil, J. A., Tan, J. P., Rudraraju, R., Mohenska, M., Sun, Y. B. Y., Walters, E., Bediaga, N. G., Sun, G., Zhou, Y., Li, Y., Drew, D., Pymm, P., Tham, W. H., Rossello, F. J., Nie, G., Liu, X., Subbarao, K., & Polo, J. M. (2023). A placental model of SARS-CoV-2 infection reveals ACE2-dependent susceptibility and differentiation impairment in syncytiotrophoblasts. Nature Cell Biology, 25(8), 1223-1234. https://doi.org/10.1038/s41556-023-01182-0

@article{7761b6cc27284efc8032c94187ea3957,

title = "A placental model of SARS-CoV-2 infection reveals ACE2-dependent susceptibility and differentiation impairment in syncytiotrophoblasts",

abstract = "SARS-CoV-2 infection causes COVID-19. Several clinical reports have linked COVID-19 during pregnancy to negative birth outcomes and placentitis. However, the pathophysiological mechanisms underpinning SARS-CoV-2 infection during placentation and early pregnancy are not clear. Here, to shed light on this, we used induced trophoblast stem cells to generate an in vitro early placenta infection model. We identified that syncytiotrophoblasts could be infected through angiotensin-converting enzyme 2 (ACE2). Using a co-culture model of vertical transmission, we confirmed the ability of the virus to infect syncytiotrophoblasts through a previous endometrial cell infection. We further demonstrated transcriptional changes in infected syncytiotrophoblasts that led to impairment of cellular processes, reduced secretion of HCG hormone and morphological changes vital for syncytiotrophoblast function. Furthermore, different antibody strategies and antiviral drugs restore these impairments. In summary, we have established a scalable and tractable platform to study early placental cell types and highlighted its use in studying strategies to protect the placenta.",

author = "J. Chen and Neil, {J. A.} and Tan, {J. P.} and R. Rudraraju and M. Mohenska and Sun, {Y. B.Y.} and E. Walters and Bediaga, {N. G.} and G. Sun and Y. Zhou and Y. Li and D. Drew and P. Pymm and Tham, {W. H.} and Rossello, {F. J.} and G. Nie and X. Liu and K. Subbarao and Polo, {J. M.}",

note = "Publisher Copyright: {\textcopyright} 2023, The Author(s).",

year = "2023",

doi = "10.1038/s41556-023-01182-0",

language = "English",

volume = "25",

pages = "1223--1234",

journal = "Nature Cell Biology",

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Chen, J, Neil, JA, Tan, JP, Rudraraju, R, Mohenska, M, Sun, YBY, Walters, E, Bediaga, NG, Sun, G, Zhou, Y, Li, Y, Drew, D, Pymm, P, Tham, WH, Rossello, FJ, Nie, G, Liu, X, Subbarao, K & Polo, JM 2023, 'A placental model of SARS-CoV-2 infection reveals ACE2-dependent susceptibility and differentiation impairment in syncytiotrophoblasts', Nature Cell Biology, vol. 25, no. 8, pp. 1223-1234. https://doi.org/10.1038/s41556-023-01182-0

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T1 - A placental model of SARS-CoV-2 infection reveals ACE2-dependent susceptibility and differentiation impairment in syncytiotrophoblasts

AU - Chen, J.

AU - Neil, J. A.

AU - Tan, J. P.

AU - Rudraraju, R.

AU - Mohenska, M.

AU - Sun, Y. B.Y.

AU - Walters, E.

AU - Bediaga, N. G.

AU - Sun, G.

AU - Zhou, Y.

AU - Li, Y.

AU - Drew, D.

AU - Pymm, P.

AU - Tham, W. H.

AU - Rossello, F. J.

AU - Nie, G.

AU - Liu, X.

AU - Subbarao, K.

AU - Polo, J. M.

PY - 2023

Y1 - 2023

N2 - SARS-CoV-2 infection causes COVID-19. Several clinical reports have linked COVID-19 during pregnancy to negative birth outcomes and placentitis. However, the pathophysiological mechanisms underpinning SARS-CoV-2 infection during placentation and early pregnancy are not clear. Here, to shed light on this, we used induced trophoblast stem cells to generate an in vitro early placenta infection model. We identified that syncytiotrophoblasts could be infected through angiotensin-converting enzyme 2 (ACE2). Using a co-culture model of vertical transmission, we confirmed the ability of the virus to infect syncytiotrophoblasts through a previous endometrial cell infection. We further demonstrated transcriptional changes in infected syncytiotrophoblasts that led to impairment of cellular processes, reduced secretion of HCG hormone and morphological changes vital for syncytiotrophoblast function. Furthermore, different antibody strategies and antiviral drugs restore these impairments. In summary, we have established a scalable and tractable platform to study early placental cell types and highlighted its use in studying strategies to protect the placenta.

AB - SARS-CoV-2 infection causes COVID-19. Several clinical reports have linked COVID-19 during pregnancy to negative birth outcomes and placentitis. However, the pathophysiological mechanisms underpinning SARS-CoV-2 infection during placentation and early pregnancy are not clear. Here, to shed light on this, we used induced trophoblast stem cells to generate an in vitro early placenta infection model. We identified that syncytiotrophoblasts could be infected through angiotensin-converting enzyme 2 (ACE2). Using a co-culture model of vertical transmission, we confirmed the ability of the virus to infect syncytiotrophoblasts through a previous endometrial cell infection. We further demonstrated transcriptional changes in infected syncytiotrophoblasts that led to impairment of cellular processes, reduced secretion of HCG hormone and morphological changes vital for syncytiotrophoblast function. Furthermore, different antibody strategies and antiviral drugs restore these impairments. In summary, we have established a scalable and tractable platform to study early placental cell types and highlighted its use in studying strategies to protect the placenta.

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JO - Nature Cell Biology

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ER -

A placental model of SARS-CoV-2 infection reveals ACE2-dependent susceptibility and differentiation impairment in syncytiotrophoblasts

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