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Placental Expression of ACE2 and TMPRSS2 in Maternal Severe Acute Respiratory Syndrome Coronavirus 2 Infection: Are Placental Defenses Mediated by Fetal Sex?
J Infect Dis. 2021 12 08; 224(Suppl 6):S647-S659.JI

Abstract

BACKGROUND

Expression of angiotensin-converting enzyme 2 (ACE2) and type II transmembrane serine protease (TMPRSS2), host molecules required for viral entry, may underlie sex differences in vulnerability to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We investigated whether placental ACE2 and TMPRSS2 expression vary by fetal sex in the presence of maternal SARS-CoV-2 infection.

METHODS

Placental ACE2 and TMPRSS2 expression was quantified by quantitative reverse transcription polymerase chain reaction (RT-PCR) and by Western blot in 68 pregnant women (38 SARS-CoV-2 positive, 30 SARS-CoV-2 negative) delivering at Mass General Brigham from April to June 2020. The impact of fetal sex and maternal SARS-CoV-2 exposure on ACE2 and TMPRSS2 was analyzed by 2-way analysis of variance (ANOVA).

RESULTS

Maternal SARS-CoV-2 infection impacted placental TMPRSS2 expression in a sexually dimorphic fashion (2-way ANOVA interaction, P = .002). We observed no impact of fetal sex or maternal SARS-CoV-2 status on ACE2. TMPRSS2 expression was significantly correlated with ACE2 expression in males (Spearman ρ = 0.54, P = .02) but not females (ρ = 0.23, P = .34) exposed to maternal SARS-CoV-2.

CONCLUSIONS

Sex differences in placental TMPRSS2 but not ACE2 were observed in the setting of maternal SARS-CoV-2 infection, which may have implications for offspring vulnerability to placental infection.

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Authors+Show Affiliations

Shook LL
Department of Obstetrics and Gynecology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA. Vincent Center for Reproductive Biology, Massachusetts General Hospital, Boston, Massachusetts, USA.
Bordt EA
Department of Pediatrics, Lurie Center for Autism, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Meinsohn MC
Pediatric Surgical Research Laboratories, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Pepin D
Pediatric Surgical Research Laboratories, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
De Guzman RM
Department of Obstetrics and Gynecology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA. Vincent Center for Reproductive Biology, Massachusetts General Hospital, Boston, Massachusetts, USA.
Brigida S
Department of Obstetrics and Gynecology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA. Vincent Center for Reproductive Biology, Massachusetts General Hospital, Boston, Massachusetts, USA.
Yockey LJ
Department of Obstetrics and Gynecology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA. Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
James KE
Department of Obstetrics and Gynecology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Sullivan MW
Department of Obstetrics and Gynecology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Bebell LM
Division of Infectious Diseases, Massachusetts General Hospital, MGH Center for Global Health, and Harvard Medical School, Boston, Massachusetts, USA.
Roberts DJ
Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Kaimal AJ
Department of Obstetrics and Gynecology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Li JZ
Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Schust D
Department of Obstetrics, Gynecology, and Women's Health, University of Missouri, Columbia, Missouri, USA.
Gray KJ
Department of Obstetrics and Gynecology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Edlow AG
Department of Obstetrics and Gynecology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA. Vincent Center for Reproductive Biology, Massachusetts General Hospital, Boston, Massachusetts, USA.

MeSH

AdultAngiotensin-Converting Enzyme 2COVID-19FemaleFetal BloodFetusGene ExpressionHumansInfectious Disease Transmission, VerticalMalePlacentaPregnancyPregnancy Complications, InfectiousSARS-CoV-2Serine EndopeptidasesSex Factors

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

34293137

Citation

Shook, Lydia L., et al. "Placental Expression of ACE2 and TMPRSS2 in Maternal Severe Acute Respiratory Syndrome Coronavirus 2 Infection: Are Placental Defenses Mediated By Fetal Sex?" The Journal of Infectious Diseases, vol. 224, no. Suppl 6, 2021, pp. S647-S659.
Shook LL, Bordt EA, Meinsohn MC, et al. Placental Expression of ACE2 and TMPRSS2 in Maternal Severe Acute Respiratory Syndrome Coronavirus 2 Infection: Are Placental Defenses Mediated by Fetal Sex? J Infect Dis. 2021;224(Suppl 6):S647-S659.
Shook, L. L., Bordt, E. A., Meinsohn, M. C., Pepin, D., De Guzman, R. M., Brigida, S., Yockey, L. J., James, K. E., Sullivan, M. W., Bebell, L. M., Roberts, D. J., Kaimal, A. J., Li, J. Z., Schust, D., Gray, K. J., & Edlow, A. G. (2021). Placental Expression of ACE2 and TMPRSS2 in Maternal Severe Acute Respiratory Syndrome Coronavirus 2 Infection: Are Placental Defenses Mediated by Fetal Sex? The Journal of Infectious Diseases, 224(Suppl 6), S647-S659. https://doi.org/10.1093/infdis/jiab335
Shook LL, et al. Placental Expression of ACE2 and TMPRSS2 in Maternal Severe Acute Respiratory Syndrome Coronavirus 2 Infection: Are Placental Defenses Mediated By Fetal Sex. J Infect Dis. 2021 12 8;224(Suppl 6):S647-S659. PubMed PMID: 34293137.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Placental Expression of ACE2 and TMPRSS2 in Maternal Severe Acute Respiratory Syndrome Coronavirus 2 Infection: Are Placental Defenses Mediated by Fetal Sex? AU - Shook,Lydia L, AU - Bordt,Evan A, AU - Meinsohn,Marie-Charlotte, AU - Pepin,David, AU - De Guzman,Rose M, AU - Brigida,Sara, AU - Yockey,Laura J, AU - James,Kaitlyn E, AU - Sullivan,Mackenzie W, AU - Bebell,Lisa M, AU - Roberts,Drucilla J, AU - Kaimal,Anjali J, AU - Li,Jonathan Z, AU - Schust,Danny, AU - Gray,Kathryn J, AU - Edlow,Andrea G, PY - 2021/7/23/pubmed PY - 2021/12/21/medline PY - 2021/7/22/entrez KW - COVID-19 KW - SARS-CoV-2 KW - angiotensin-converting enzyme 2 KW - infection KW - placenta KW - sex differences KW - transplacental transmission KW - type II transmembrane serine protease KW - vertical transmission SP - S647 EP - S659 JF - The Journal of infectious diseases JO - J Infect Dis VL - 224 IS - Suppl 6 N2 - BACKGROUND: Expression of angiotensin-converting enzyme 2 (ACE2) and type II transmembrane serine protease (TMPRSS2), host molecules required for viral entry, may underlie sex differences in vulnerability to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We investigated whether placental ACE2 and TMPRSS2 expression vary by fetal sex in the presence of maternal SARS-CoV-2 infection. METHODS: Placental ACE2 and TMPRSS2 expression was quantified by quantitative reverse transcription polymerase chain reaction (RT-PCR) and by Western blot in 68 pregnant women (38 SARS-CoV-2 positive, 30 SARS-CoV-2 negative) delivering at Mass General Brigham from April to June 2020. The impact of fetal sex and maternal SARS-CoV-2 exposure on ACE2 and TMPRSS2 was analyzed by 2-way analysis of variance (ANOVA). RESULTS: Maternal SARS-CoV-2 infection impacted placental TMPRSS2 expression in a sexually dimorphic fashion (2-way ANOVA interaction, P = .002). We observed no impact of fetal sex or maternal SARS-CoV-2 status on ACE2. TMPRSS2 expression was significantly correlated with ACE2 expression in males (Spearman ρ = 0.54, P = .02) but not females (ρ = 0.23, P = .34) exposed to maternal SARS-CoV-2. CONCLUSIONS: Sex differences in placental TMPRSS2 but not ACE2 were observed in the setting of maternal SARS-CoV-2 infection, which may have implications for offspring vulnerability to placental infection. SN - 1537-6613 UR - https://www.unboundmedicine.com/medline/citation/34293137/Placental_Expression_of_ACE2_and_TMPRSS2_in_Maternal_Severe_Acute_Respiratory_Syndrome_Coronavirus_2_Infection:_Are_Placental_Defenses_Mediated_by_Fetal_Sex DB - PRIME DP - Unbound Medicine ER -