SARS-CoV-2 infection risk assessment in the endometrium: viral infection-related gene expression across the menstrual cycle

Expression of SARS-CoV-2 infection-related genes in the endometrium show different risks of infection de- pending on menstrual cycle phases, women’s age, and viral cell entry mechanisms.

VOLUME 114, ISSUE 2, P223-232


Ismael Henarejos-Castillo, M.Sc., Patricia Sebastian-Leon, Ph.D., Almudena Devesa-Peiro, M.Sc., Antonio Pellicer, M.D., Ph.D., Patricia Diaz-Gimeno, Ph.D.



To determine the susceptibility of the endometrium to infection by—and thereby potential damage from—SARS-CoV-2.


Analysis of SARS-Cov-2 infection-related gene expression from endometrial transcriptomic data sets.


Infertility research department affiliated with a public hospital.


Gene expression data from five studies in 112 patients with normal endometrium collected throughout the menstrual cycle.



Main Outcome Measure(s)

Gene expression and correlation between viral infectivity genes and age throughout the menstrual cycle.


Gene expression was high for TMPRSS4, CTSL, CTSB, FURIN, MX1, and BSG; medium for TMPRSS2; and low for ACE2. ACE2, TMPRSS4, CTSB, CTSL, and MX1 expression increased toward the window of implantation. TMPRSS4 expression was positively correlated with ACE2, CTSB, CTSL, MX1, and FURIN during several cycle phases; TMPRSS2 was not statistically significantly altered across the cycle. ACE2, TMPRSS4, CTSB, CTSL, BSG, and MX1 expression increased with age, especially in early phases of the cycle.


Endometrial tissue is likely safe from SARS-CoV-2 cell entry based on ACE2 and TMPRSS2 expression, but susceptibility increases with age. Further, TMPRSS4, along with BSG-mediated viral entry into cells, could imply a susceptible environment for SARS-CoV-2 entry via different mechanisms. Additional studies are warranted to determine the true risk of endometrial infection by SARS-CoV-2 and implications for fertility treatments.

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