TY - JOUR T1 - Placental expression of ACE2 and TMPRSS2 in maternal SARS-CoV-2 infection: are placental defenses mediated by fetal sex? JF - bioRxiv DO - 10.1101/2021.04.01.438089 SP - 2021.04.01.438089 AU - Lydia L Shook AU - Evan A Bordt AU - Marie-Charlotte Meinsohn AU - David Pepin AU - Rose M De Guzman AU - Sara Brigida AU - Laura J Yockey AU - Kaitlyn E James AU - Mackenzie W Sullivan AU - Lisa M Bebell AU - Drucilla J Roberts AU - Anjali J Kaimal AU - Jonathan Z Li AU - Danny Schust AU - Kathryn J Gray AU - Andrea G Edlow Y1 - 2021/01/01 UR - http://biorxiv.org/content/early/2021/04/01/2021.04.01.438089.abstract N2 - Background Sex differences in vulnerability to and severity of SARS-CoV-2 infection have been described in non-pregnant populations. ACE2 and TMPRSS2, host molecules required for viral entry, are regulated by sex steroids and expressed in the placenta. We sought to investigate whether placental ACE2 and TMPRSS2 expression vary by fetal sex and in the presence of maternal SARS-CoV-2 infection.Methods Placental ACE2 and TMPRSS2 were quantified in 68 pregnant individuals (38 SARS-CoV-2 positive, 30 SARS-CoV-2 negative) delivering at Mass General Brigham from April to June 2020. Maternal SARS-CoV-2 status was determined by nasopharyngeal RT-PCR. Placental SARS-CoV-2 viral load was quantified. RTqPCR was performed to quantify expression of ACE2 and TMPRSS2 relative to the reference gene YWHAZ. Western blots were performed on placental homogenates to quantify protein levels. The impact of fetal sex and SARS-CoV-2 exposure on ACE2 and TMPRSS2 expression was analyzed by 2-way ANOVA.Results SARS-CoV-2 virus was undetectable in all placentas. Maternal SARS-CoV-2 infection impacted TMPRSS2 placental gene and protein expression in a sexually dimorphic fashion (2-way ANOVA interaction p-value: 0.002). We observed no impact of fetal sex or maternal SARS-CoV-2 status on placental ACE2 gene or protein expression. Placental TMPRSS2 expression was significantly correlated with ACE2 expression in males (Spearman’s ρ=0.54, p=0.02) but not females (ρ=0.23, p=0.34) 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. These findings may have implications for offspring vulnerability to placental infection and vertical transmission.These findings may have implications for offspring vulnerability to placental infection and vertical transmission.Competing Interest StatementThe authors have declared no competing interest.(ACE2)Angiotensin-Converting Enzyme 2(TMPRSS2)Type II Transmembrane Serine Protease(YWHAZ)Tyrosine 3-Monooxygenase/Tryptophan 5-Monooxygenase Activation Protein Zeta(RAAS)renin-angiotensin-aldosterone system ER -