SARS-CoV-2 and Implantation Window: Gene Expression Mapping of Human Endometrium and Preimplantation Embryo.

Delphine Haouzi,Frida Entezami,Alain R. Thierry,Samir Hamamah,Sophie Brouillet,Anna Gala,Alice Ferrières-Hoa,Edward Tuaillon

doi:10.3390/life11121378

Abstract

Understanding whether SARS-CoV-2 could infect cells and tissues handled during ART is crucial for risk mitigation, especially during the implantation window when either endometrial biopsies are often practiced for endometrial receptivity assessment or embryo transfer is performed. To address this question, this review analyzed current knowledge of the field and retrospectively examined the gene expression profiles of SARS-CoV-2-associated receptors and proteases in a cohort of ART candidates using our previous Affymetrix microarray data. Human endometrial tissue under natural and controlled ovarian stimulation cycles and preimplantation embryos were analyzed. A focus was particularly drawn on the renin-angiotensin system, which plays a prominent role in the virus infection, and we compared the gene expression levels of receptors and proteases related to SARS-CoV-2 infection in the samples. High prevalence of genes related to the ACE2 pathway during both cycle phases and mainly during the mid-secretory phase for ACE2 were reported. The impact of COS protocols on endometrial gene expression profile of SARS-CoV-2-associated receptors and proteases is minimal, suggesting no additional potential risks during stimulated ART procedure. In blastocysts, ACE2, BSG, CTSL, CTSA and FURIN were detectable in the entire cohort at high expression level. Specimens from female genital tract should be considered as potential targets for SARS-CoV-2, especially during the implantation window.

Highlights

SARS-CoV-2 infection has been surprising by its symptoms, sometime atypical, and ranging from minimal forms to life-threatening distress
The endometrial receptivity assessment is under investigation during assisted reproductive technologies (ART) practice, especially in patients with repeated implantation failures (RIF), for whom it was shown to be useful in some reports
The present study aimed to assess the expression level of genes related to the angiotensinconverting enzyme 2 (ACE2) pathway and other alternative pathways (TMPRSS2, BSG, CTSL, CTSA, FURIN), known as targets for SARS-CoV-2 cell entry [6,10,21]

Summary

Introduction

SARS-CoV-2 infection has been surprising by its symptoms, sometime atypical, and ranging from minimal forms to life-threatening distress. Identification of potential organ/cell targets for SARS-CoV-2 infection presents a challenge during the pandemic, especially in the scarcely explored field of assisted reproductive technologies (ART). To address this issue, some recent studies focused on the transcriptomic and/or proteomic profiling of SARS-CoV-2-associated receptors and proteases related to the virus infection in different human tissues [4]. No studies have analyzed the potential impact of COS protocols during ART procedure on the gene expression profiles of SARS-CoV-2-associated receptors and proteases in parallel in human endometrial tissues and in preimplantation embryos during the implantation window. As during ART, various cells and tissues, such as embryos and endometrial tissues, are handled and/or manipulated in the laboratory for the purpose of treatment or diagnosis; the investigation of SARS-CoV-2 host entry candidates in endometrial tissues from patients recruited for endometrial receptivity appreciation during the theoretical implantation window using the win-Test [14], and in preimplantation embryos, deserves investigation

Objectives

Methods

Results

Conclusion