Is SARS-CoV-2 Infection a Risk Factor for Early Pregnancy Loss? ACE2 and TMPRSS2 Coexpression and Persistent Replicative Infection in Primitive Trophoblast
| Autor: | Andrea G. Edlow, H Liu, Yuchen Tian, R. M. Roberts, Toshihiko Ezashi, Wenjun Ma, Sehee Choi, Jie Zhou, J Zhang, Danny J. Schust |
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| Rok vydání: | 2021 |
| Předmět: |
Adult
placenta Early Pregnancy Loss miscarriage ACE2 Biology Miscarriage Syncytiotrophoblast Pregnancy Risk Factors Placenta medicine Immunology and Allergy Humans Pregnancy Complications Infectious reproductive and urinary physiology TMPRSS2 SARS-CoV-2 Serine Endopeptidases Trophoblast COVID-19 medicine.disease Embryonic stem cell trophoblast Trophoblasts Abortion Spontaneous stem cell Infectious Diseases medicine.anatomical_structure AcademicSubjects/MED00290 spontaneous abortion Immunology embryonic structures Placental Science Supplement Female Persistent Infection Angiotensin-Converting Enzyme 2 Stem cell |
| Zdroj: | The Journal of Infectious Diseases |
| ISSN: | 1537-6613 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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