FEMALE GAMETE AND HUMAN EMBRYO SUSCEPTIBILITY TO SARS-COV-2

Abstract

Objective: To determine the susceptibility of the oocytes, embryos, granulosa and cumulus cells to SARS-CoV-2 infection. Materials and Methods: To address this question, we retrospectively examined the gene expression profiles of SARS-CoV-2-associated receptors and proteases in human granulosa cells (GCs), cumulus cells (CCs), mature oocytes, day 3 embryos, blastocysts and trophectoderm cells obtained from our previously described Affymetrix microarray data from assisted reproduction patients. Human GCs and CCs (n=17), mature oocytes (n=6), and preimplantation embryos (n=20) were analyzed and gene expression levels of receptors and proteases closely related to SARS-CoV-2 infection was reported. For each gene, the number of samples with the probe set 'present', based on the detection call was studied. Each probe set was classified according to the signal intensity value median, as low ( 200). Results: ACE2, BSG, CTSL, CTSA were detectable at high expression level in all mature oocyte samples, while only CTSL was strongly expressed in all day 3 embryos. The most representative dual co-expression of SARS-CoV-2-associated receptor and protease (60% of samples) during the embryonic genome activation stage (EGA) was ACE2-CTSL and BSG-CTSL. In blastocysts, ACE2, BSG, CTSL, CTSA and FURIN were detectable in the entire cohort at high expression level, and the prevalence of the different dual co-expression of SARS-CoV-2-associated proteases and receptors was optimal (100% of samples). Interestingly, only CTSL was detectable in all trophectoderm samples and a prevalence of 60% was found for the BSG-CTSL co-expression. ACE2, BSG, CTSL and CTSA were present at high expression level in CCs samples. In contrast, ACE2 and BSG expression was very low while CTSL and CTSA showed a high expression level in GCs. A prevalence of 100% was reported for ACE2-CTSL, ACE2-CTSA co-expression for both cell types. In addition, BSG-CTSL and BSG-CTSA co-expression were also present in all CCs against ∼70% in GCs samples. This data suggests a potential risk of SARS-CoV-2 infection either GC or early embryo development. Conclusions: Transcriptomic analyses of SARS-CoV-2-associated receptors and proteases strongly suggest that blastocysts are most permissive to SARS-CoV-2 compared with mature oocytes and day 3 embryos. Impact Statement: Specimens from female genital tract may be considered as potential targets for SARS-CoV-2.