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Is SARS-CoV-2 infection a risk factor for early pregnancy loss? ACE2 and TMPRSS2 co-expression and persistent replicative infection in primitive trophoblast.
J Infect Dis. 2021 Jul 22 [Online ahead of print]JI

Abstract

BACKGROUND

SARS-CoV-2 infection in term placenta is relatively 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. Infections of the peri-implantation placenta 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-derived model of peri-implantation placental development to assess patterns of ACE2 and TMPRSS2 transcription and protein expression in primitive trophoblast. These molecules are involved in SARS-CoV-2 cell entry and infection. 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 stem-cell derived trophoblast, with preferential expression in syncytialized cells. These same syncytialized 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 early human embryonic stem cell-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. Potential implications of these findings for early pregnancy loss deserve further investigation.

Authors+Show Affiliations

Department of Obstetrics, Gynecology and Women's Health, University of Missouri School of Medicine, Columbia, MO USA. Christopher S Bond Life Sciences Center, University of Missouri, Columbia, MO 65211 USA.Department of Obstetrics, Gynecology and Women's Health, University of Missouri School of Medicine, Columbia, MO USA. Christopher S Bond Life Sciences Center, University of Missouri, Columbia, MO 65211 USA.Department of Molecular Microbiology and Immunology, School of Medicine, University of Missouri, Columbia, MO USA. Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Missouri, Columbia, MO USA.Department of Molecular Microbiology and Immunology, School of Medicine, University of Missouri, Columbia, MO USA. Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Missouri, Columbia, MO USA.Christopher S Bond Life Sciences Center, University of Missouri, Columbia, MO 65211 USA. Division of Animal Sciences, Bond Life Sciences Center, University of Missouri, Columbia, MO, USA.Department of Obstetrics and Gynecology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. Vincent Center for Reproductive Biology, Massachusetts General Hospital, Boston, MA, USA.Christopher S Bond Life Sciences Center, University of Missouri, Columbia, MO 65211 USA. Division of Animal Sciences, Bond Life Sciences Center, University of Missouri, Columbia, MO, USA.Christopher S Bond Life Sciences Center, University of Missouri, Columbia, MO 65211 USA. Division of Animal Sciences, Bond Life Sciences Center, University of Missouri, Columbia, MO, USA.Department of Molecular Microbiology and Immunology, School of Medicine, University of Missouri, Columbia, MO USA. Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Missouri, Columbia, MO USA.Department of Obstetrics, Gynecology and Women's Health, University of Missouri School of Medicine, Columbia, MO USA.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

34293134

Citation

Zhou, J, et al. "Is SARS-CoV-2 Infection a Risk Factor for Early Pregnancy Loss? ACE2 and TMPRSS2 Co-expression and Persistent Replicative Infection in Primitive Trophoblast." The Journal of Infectious Diseases, 2021.
Zhou J, Choi S, Liu H, et al. Is SARS-CoV-2 infection a risk factor for early pregnancy loss? ACE2 and TMPRSS2 co-expression and persistent replicative infection in primitive trophoblast. J Infect Dis. 2021.
Zhou, J., Choi, S., Liu, H., Zhang, J., Tian, Y., Edlow, A. G., Ezashi, T., Roberts, R. M., Ma, W., & Schust, D. J. (2021). Is SARS-CoV-2 infection a risk factor for early pregnancy loss? ACE2 and TMPRSS2 co-expression and persistent replicative infection in primitive trophoblast. The Journal of Infectious Diseases. https://doi.org/10.1093/infdis/jiab309
Zhou J, et al. Is SARS-CoV-2 Infection a Risk Factor for Early Pregnancy Loss? ACE2 and TMPRSS2 Co-expression and Persistent Replicative Infection in Primitive Trophoblast. J Infect Dis. 2021 Jul 22; PubMed PMID: 34293134.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Is SARS-CoV-2 infection a risk factor for early pregnancy loss? ACE2 and TMPRSS2 co-expression and persistent replicative infection in primitive trophoblast. AU - Zhou,J, AU - Choi,S, AU - Liu,H, AU - Zhang,J, AU - Tian,Y, AU - Edlow,A G, AU - Ezashi,T, AU - Roberts,R M, AU - Ma,W, AU - Schust,D J, Y1 - 2021/07/22/ PY - 2021/04/23/received PY - 2021/7/22/entrez PY - 2021/7/23/pubmed PY - 2021/7/23/medline KW - ACE2 KW - COVID-19 KW - SARS-CoV-2 KW - TMPRSS2 KW - miscarriage KW - placenta KW - spontaneous abortion KW - stem cell KW - trophoblast JF - The Journal of infectious diseases JO - J Infect Dis N2 - BACKGROUND: SARS-CoV-2 infection in term placenta is relatively 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. Infections of the peri-implantation placenta 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-derived model of peri-implantation placental development to assess patterns of ACE2 and TMPRSS2 transcription and protein expression in primitive trophoblast. These molecules are involved in SARS-CoV-2 cell entry and infection. 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 stem-cell derived trophoblast, with preferential expression in syncytialized cells. These same syncytialized 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 early human embryonic stem cell-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. Potential implications of these findings for early pregnancy loss deserve further investigation. SN - 1537-6613 UR - https://www.unboundmedicine.com/medline/citation/34293134/Is_SARS-CoV-2_infection_a_risk_factor_for_early_pregnancy_loss_ACE2_and_TMPRSS2_co-expression_and_persistent_replicative_infection_in_primitive_trophoblast. L2 - https://academic.oup.com/jid/article-lookup/doi/10.1093/infdis/jiab309 DB - PRIME DP - Unbound Medicine ER -
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