Shook, Lydia LBordt, Evan AMeinsohn, Marie-CharlottePepin, DavidDe Guzman, Rose MBrigida, SaraYockey, Laura JJames, Kaitlyn ESullivan, Mackenzie WBebell, Lisa MRoberts, Drucilla JKaimal, Anjali JLi, Jonathan ZSchust, DannyGray, Kathryn JEdlow, Andrea G2023-06-122023-06-122021-120022-18991537-6613https://hdl.handle.net/10161/27901<h4>Background</h4>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.<h4>Methods</h4>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).<h4>Results</h4>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.<h4>Conclusions</h4>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.Fetal BloodFetusPlacentaHumansPregnancy Complications, InfectiousSerine EndopeptidasesSex FactorsGene ExpressionPregnancyAdultFemaleMaleInfectious Disease Transmission, VerticalCOVID-19Angiotensin-Converting Enzyme 2SARS-CoV-2Journal article2023-06-12