Placental Expression of ACE2 and TMPRSS2 in Maternal Severe Acute Respiratory Syndrome Coronavirus 2 Infection: Are Placental Defenses Mediated by Fetal Sex?
Adult
Angiotensin-Converting Enzyme 2
/ metabolism
COVID-19
/ blood
Female
Fetal Blood
/ immunology
Fetus
/ virology
Gene Expression
Humans
Infectious Disease Transmission, Vertical
Male
Placenta
/ metabolism
Pregnancy
Pregnancy Complications, Infectious
/ virology
SARS-CoV-2
/ immunology
Serine Endopeptidases
/ metabolism
Sex Factors
COVID-19
SARS-CoV-2
angiotensin-converting enzyme 2
infection
placenta
sex differences
transplacental transmission
type II transmembrane serine protease
vertical transmission
Journal
The Journal of infectious diseases
ISSN: 1537-6613
Titre abrégé: J Infect Dis
Pays: United States
ID NLM: 0413675
Informations de publication
Date de publication:
08 12 2021
08 12 2021
Historique:
pubmed:
23
7
2021
medline:
21
12
2021
entrez:
22
7
2021
Statut:
ppublish
Résumé
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. 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). 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. 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.
Sections du résumé
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.
Identifiants
pubmed: 34293137
pii: 6325592
doi: 10.1093/infdis/jiab335
pmc: PMC8344531
doi:
Substances chimiques
ACE2 protein, human
EC 3.4.17.23
Angiotensin-Converting Enzyme 2
EC 3.4.17.23
Serine Endopeptidases
EC 3.4.21.-
TMPRSS2 protein, human
EC 3.4.21.-
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
S647-S659Subventions
Organisme : Claflin Award from the Massachusetts General Hospital Executive Committee on Research
Organisme : NIMH NIH HHS
ID : U54 MH118919
Pays : United States
Organisme : NICHD NIH HHS
ID : K12 HD103096
Pays : United States
Organisme : NHLBI NIH HHS
ID : K08 HL146963
Pays : United States
Organisme : NIMH NIH HHS
ID : F32 MH116604
Pays : United States
Organisme : NICHD NIH HHS
ID : R01 HD100022
Pays : United States
Organisme : Eunice Kennedy Shriver National Institute of Child Health and Human Development
ID : 1R01HD100022-01
Organisme : National Institute on Mental Health
ID : F32MH116604
Organisme : NHLBI NIH HHS
ID : K08HL1469630-02
Pays : United States
Informations de copyright
© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.
Références
Obstet Gynecol. 2020 Aug;136(2):300-302
pubmed: 32496337
Biol Sex Differ. 2010 Nov 05;1(1):6
pubmed: 21208466
Am J Obstet Gynecol. 2021 Jan;224(1):35-53.e3
pubmed: 32739398
Lancet. 2020 Aug 22;396(10250):532-533
pubmed: 32798449
Am J Physiol Lung Cell Mol Physiol. 2020 Nov 1;319(5):L843-L847
pubmed: 32996784
PLoS One. 2020 Apr 16;15(4):e0230295
pubmed: 32298273
Ann Transl Med. 2020 Sep;8(17):1077
pubmed: 33145296
Sci Transl Med. 2021 Oct 27;13(617):eabi7428
pubmed: 34664987
J Biomed Inform. 2009 Apr;42(2):377-81
pubmed: 18929686
Int J Med Sci. 2020 Jun 18;17(11):1522-1531
pubmed: 32669955
N Engl J Med. 2020 Jul 23;383(4):334-346
pubmed: 32598831
Biol Sex Differ. 2020 Sep 18;11(1):53
pubmed: 32948238
Placenta. 2008 Sep;29(9):798-801
pubmed: 18684503
Mod Pathol. 2020 Nov;33(11):2092-2103
pubmed: 32741970
JAMA Netw Open. 2020 Dec 1;3(12):e2030455
pubmed: 33351086
PLoS One. 2015 May 26;10(5):e0127515
pubmed: 26010093
Biol Reprod. 2012 Feb 09;86(2):31
pubmed: 22011389
Eur Urol. 2020 Aug;78(2):296-298
pubmed: 32418620
Life Sci. 2006 Apr 4;78(19):2166-71
pubmed: 16303146
Signal Transduct Target Ther. 2021 Mar 1;6(1):100
pubmed: 33649313
Eur J Clin Microbiol Infect Dis. 2021 Feb;40(2):451-455
pubmed: 33245471
Hypertension. 2001 May;37(5):1199-208
pubmed: 11358929
JAMA. 2020 Jun 16;323(23):2427-2429
pubmed: 32432657
Am J Physiol Heart Circ Physiol. 2021 Jan 1;320(1):H296-H304
pubmed: 33275517
Signal Transduct Target Ther. 2020 May 21;5(1):71
pubmed: 32435059
Engineering (Beijing). 2020 Oct;6(10):1162-1169
pubmed: 32837754
Ultrasound Obstet Gynecol. 2021 Apr;57(4):573-581
pubmed: 33620113
Curr Opin Pharmacol. 2006 Jun;6(3):271-6
pubmed: 16581295
MMWR Morb Mortal Wkly Rep. 2020 Apr 10;69(14):422-426
pubmed: 32271728
Am J Obstet Gynecol. 2020 Aug;223(2):275-278
pubmed: 32405074
Oncogene. 2020 Sep;39(37):5950-5963
pubmed: 32778768
Ann Oncol. 2020 Aug;31(8):1040-1045
pubmed: 32387456
J Clin Invest. 2020 Sep 1;130(9):4947-4953
pubmed: 32573498
Med Hypotheses. 2020 Nov;144:110271
pubmed: 33254575
Cancer Discov. 2014 Nov;4(11):1310-25
pubmed: 25122198
Virology. 2019 Nov;537:226-236
pubmed: 31539770
Nat Commun. 2020 Nov 30;11(1):6122
pubmed: 33257679
Nat Commun. 2020 Oct 12;11(1):5139
pubmed: 33046696
Eur Heart J. 2020 May 14;41(19):1810-1817
pubmed: 32388565
Prog Urol. 2020 Sep;30(10):484-487
pubmed: 32620366
J Endocrinol Invest. 2021 May;44(5):951-956
pubmed: 32936429
Nat Immunol. 2021 Jan;22(1):32-40
pubmed: 33277638
Nat Commun. 2020 Oct 30;11(1):5493
pubmed: 33127906
Demography. 2013 Apr;50(2):421-44
pubmed: 23151996
Endocrinology. 2012 Jan;153(1):462-8
pubmed: 22045662
Reprod Health. 2020 Dec 17;17(Suppl 3):178
pubmed: 33334358
Reprod Biol Endocrinol. 2017 Dec 29;15(1):97
pubmed: 29321064
Cells. 2020 Jul 25;9(8):
pubmed: 32722449
Prehosp Disaster Med. 2020 Aug;35(4):438-441
pubmed: 32600476
Nat Commun. 2020 Jul 14;11(1):3572
pubmed: 32665677
Nat Rev Immunol. 2016 Oct;16(10):626-38
pubmed: 27546235
Cancer Discov. 2020 Jun;10(6):779-782
pubmed: 32276929
MMWR Morb Mortal Wkly Rep. 2020 Nov 06;69(44):1635-1640
pubmed: 33151917
J Infect Dis. 2015 Oct 15;212(8):1214-21
pubmed: 25904605
Clin Sci (Lond). 2019 Jan 8;133(1):55-74
pubmed: 30622158
Mol Ther Methods Clin Dev. 2020 May 22;18:1-6
pubmed: 32537478
Am J Respir Crit Care Med. 2020 Jun 15;201(12):1557-1559
pubmed: 32329629
Commun Biol. 2020 Jul 8;3(1):374
pubmed: 32641750
Genome Res. 2017 Mar;27(3):349-361
pubmed: 28174237
JAMA. 2020 Jun 2;323(21):2198-2200
pubmed: 32352491
BMJ. 2020 May 22;369:m1966
pubmed: 32444366
Placenta. 2005 Sep-Oct;26(8-9):601-7
pubmed: 16085039
Placenta. 2016 Dec;48:133-135
pubmed: 27871465
Am J Obstet Gynecol MFM. 2020 Aug;2(3):100145
pubmed: 32427221
BMC Med Res Methodol. 2020 Aug 26;20(1):215
pubmed: 32842979
Redox Biol. 2020 Sep;36:101615
pubmed: 32863223
Nat Commun. 2020 Dec 9;11(1):6317
pubmed: 33298944
J Cardiovasc Pharmacol Ther. 2021 Mar;26(2):114-118
pubmed: 33078623
Nat Rev Immunol. 2020 Jul;20(7):442-447
pubmed: 32528136
Front Cell Infect Microbiol. 2020 Jun 09;10:327
pubmed: 32582576
Sci Rep. 2021 May 6;11(1):9658
pubmed: 33958627
Pediatr Infect Dis J. 2020 Sep;39(9):e265-e267
pubmed: 32658097
Gastroenterology. 2021 Jan;160(1):287-301.e20
pubmed: 32980345
J Med Virol. 2020 Jul;92(7):726-730
pubmed: 32221983
Cell Host Microbe. 2021 Jul 14;29(7):1052-1062
pubmed: 34022154
Am J Obstet Gynecol. 2021 Mar;224(3):298.e1-298.e8
pubmed: 32853537
Infect Dis Poverty. 2020 Apr 28;9(1):45
pubmed: 32345362
Nat Commun. 2020 Oct 12;11(1):5128
pubmed: 33046695
Lab Invest. 2018 Sep;98(9):1237-1249
pubmed: 29884907
Biomed Pharmacother. 2020 Nov;131:110748
pubmed: 33152916
Kidney Blood Press Res. 2007;30(2):67-80
pubmed: 17268203
Clin Microbiol Infect. 2021 Mar;27(3):489-490
pubmed: 33022363
Lancet Child Adolesc Health. 2020 Sep;4(9):653-661
pubmed: 32593339
Cell. 2020 Apr 16;181(2):271-280.e8
pubmed: 32142651
BMJ Open. 2020 Oct 6;10(10):e040129
pubmed: 33028563
PLoS Pathog. 2013;9(12):e1003774
pubmed: 24348248
MMWR Morb Mortal Wkly Rep. 2020 Aug 14;69(32):1074-1080
pubmed: 32790663
J Clin Pharmacol. 2020 Jul;60(7):801-807
pubmed: 32437018
J Med Virol. 2021 Jul;93(7):4205-4218
pubmed: 33638460
J Pathol. 2020 Jul;251(3):228-248
pubmed: 32418199
J Pediatr. 2020 Dec;227:45-52.e5
pubmed: 32827525
Hypertens Res. 2021 Jul;44(7):882-884
pubmed: 33536584
Elife. 2020 Jul 14;9:
pubmed: 32662421
N Engl J Med. 2008 Apr 17;358(16):1672-81
pubmed: 18420500
Aging (Albany NY). 2020 Jun 5;12(11):10087-10098
pubmed: 32501810