ANALYZE OF THE GENE EXPRESSION PROFILES OF SARS-COV-2-ASSOCIATED RECEPTORS AND PROTEASES IN HUMAN ENDOMETRIUM DURING ART PRACTICE

Objective: Covid-19 pandemic has significantly affected the assisted reproductive technology (ART) practice. Understanding whether SARS-CoV-2 could infect endometrial tissues during ART is crucial for risk mitigation. Materials and Methods: To address this question, we retrospectively examined the gene expression profile of SARS-CoV-2-associated receptors and proteases in endometrial biopsies of a cohort of ART candidates using Affymetrix microarray data. Human endometrial tissue under natural (n=62) and COS cycles (n=42) were analyzed. A focus was particularly made on the renin-angiotensin system relates genes with a prominent role in the virus infection, and gene expression levels of receptors and proteases closely related to SARS-CoV-2 infectionwas also studied. Results: Using our large cohort of endometrial samples, we reported a high prevalence of genes related to the ACE2 pathway, including AGT, AGTR1, ANPEP, CTSA, ENPEP, LNPEP, MME, NLN, THOP1, BSG and CTSL during both phases(early- and mid-secretory phase), and mainly during the mid-secretory phase for ACE2. The highest signal intensities were found for CTSA, LNPEP, MME, NLN, BSG and CTSL. The most representative of dual coexpression of SARS-CoV-2-associated receptor and protease in endometrium was BSG-CSTL and BSG-CTSA. It s also important to note high variation of SARS-CoV-2 receptors inter-patients under natural cycle.Globally, the impact of COS on endometrial gene expression profile of SARS-CoV-2-associated receptors and proteases of non Covid-19 patients is low, suggesting no additional potential risks of SARS-CoV-2 infection during stimulated ART procedure compared with natural cycles. Conclusions: Analyses of gene expression profiles ofSARS-CoV-2 host entry candidates from microarray data suggest that endometrium should be considered as potential target for SARS-CoV-2 infection. Impact Statement: Specimens from female genital tract may be considered as potential targets for SARS-CoV-2.