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

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

  • Nat Cell Biol. 2023 Jul 13. doi: 10.1038/s41556-023-01182-0.
J Chen # 1 2 3,  J A Neil # 4,  J P Tan # 1 2 3,  R Rudraraju # 4,  M Mohenska 1 2 3,  Y B Y Sun 1 2 3,  E Walters 1 2 3 5 6,  N G Bediaga 5 6,  G Sun 1 2 3,  Y Zhou 1 2 3,  Y Li 7,  D Drew 8,  P Pymm 8 9,  W H Tham 8 9,  F J Rossello 3 10,  G Nie 7,  X Liu 11 12 13 14,  K Subbarao 15 16,  J M Polo 17 18 19 20 21
Affiliations

Affiliations

  • 1 Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria, Australia.
  • 2 Development and Stem Cells Program, Monash Biomedicine Discovery Institute, Clayton, Victoria, Australia.
  • 3 Australian Regenerative Medicine Institute, Monash University, Clayton, Victoria, Australia.
  • 4 Department of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.
  • 5 Adelaide Centre for Epigenetics, Faculty of Health and Medical Sciences, The University of Adelaide, Adelaide, South Australia, Australia.
  • 6 South Australian Immunogenomics Cancer Institute, Faculty of Health and Medical Sciences, The University of Adelaide, Adelaide, South Australia, Australia.
  • 7 Implantation and Pregnancy Research Laboratory, School of Health and Biomedical Sciences, RMIT University, Melbourne, Victoria, Australia.
  • 8 Infectious Diseases and Immune Defences Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
  • 9 Department of Medical Biology, University of Melbourne, Melbourne, Victoria, Australia.
  • 10 University of Melbourne Centre for Cancer Research, The University of Melbourne, Melbourne, Victoria, Australia.
  • 11 School of Life Sciences, Westlake University, Hangzhou, China.
  • 12 Research Center for Industries of the Future, Westlake University, Hangzhou, China.
  • 13 Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, China.
  • 14 Westlake Institute for Advanced Study, Hangzhou, China.
  • 15 Department of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia. kanta.subbarao@influenzacentre.org.
  • 16 WHO Collaborating Centre for Reference and Research on Influenza, Melbourne, Victoria, Australia. kanta.subbarao@influenzacentre.org.
  • 17 Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria, Australia. jose.polo@monash.edu.
  • 18 Development and Stem Cells Program, Monash Biomedicine Discovery Institute, Clayton, Victoria, Australia. jose.polo@monash.edu.
  • 19 Australian Regenerative Medicine Institute, Monash University, Clayton, Victoria, Australia. jose.polo@monash.edu.
  • 20 Adelaide Centre for Epigenetics, Faculty of Health and Medical Sciences, The University of Adelaide, Adelaide, South Australia, Australia. jose.polo@monash.edu.
  • 21 South Australian Immunogenomics Cancer Institute, Faculty of Health and Medical Sciences, The University of Adelaide, Adelaide, South Australia, Australia. jose.polo@monash.edu.
  • # Contributed equally.
PMID: 37443288 DOI: 10.1038/s41556-023-01182-0
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.

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