COVID-19 and embryo implantation: EPSTI1 and SUGT1 participate in the dysregulation of SARS-CoV-2 on endometrial receptivity

Abstract

Objective To study the potential effect of coronavirus disease 2019 (COVID-19) on the endometrial receptivity. Methods Overlapped differentially expressed genes (DEGs) between the endometrium and the throat swabs of female patients with COVID-19 infection vs. women without COVID-19 were integrated. The expression and distribution of prioritized molecules were detected in mid-secretory phase endometrium from patients infected by COVID-19 within 30 days vs. Individuals without the infection. Serum INF-γ, LPS, TNF-α, IL-1β, IL-1α and IL-6 were detected in female patients infected by COVID-19 within 30 days vs. Individuals without the infection. In vitro decidualization of human endometrial stromal cells (T-hESCs) and human choriocarcinoma (BeWo) spheroids adhesion experiments were employed to explore the functions of the potential molecules EPSTI1 and SUGT1. Cytokines of INF-γ, LPS and IL-1β were administrated in T-hESCs and human endometrial adenocarcinoma (Ishikawa) cells, and the expression of EPSTI1 and SUGT were identified. Results The systemic disease COVID-19 altered endometrial protein expression during peri-implantation window. Epithelial stromal interaction 1 (EPSTI1), S-phase kinase-associated protein 1 (SUGT1) and RCC1-containing protein 5 (HERC5) were up-regulated in mid-secretory phase endometrium of women infected by COVID-19 within 30 days. EPSTI1 and SUGT1 impaired PRL and IGFBP1 expression stimulated by 8-Br-cAMP and MPA in T-hESCs. SUGT1 decreased the adhesion rate of BeWo spheroids to Ishikawa cells induced by E₂ and MPA. Serum INF-γ, LPS, TNF-α, IL-1β and IL-6 were elevated in female patients being infected with Covid-19 with mild or moderate symptoms. IL-1β demonstrated a sustained elevation in women infected with COVID-19 within 8–30 days. EPSTI1 was up-regulated by the administration of IL-1β, INF-γ and LPS in shikawa cells and T-hESCs. SUGT1 was up-regulated by the administration of IL-1β and LPS in shikawa cells and T-hESCs. Conclusions Endometrial decidualization and embryo adhesion function were negatively influenced by EPSTI1 and SUGT1, which were highly expressed in the mid-secretory endometrium of COVID-19-infected women. The elevation of EPSTI1 and SUGT1 in patients infected with Covid-19 maybe related to the increased cytokines of IL-1β, INF-γ and LPS. Investigating the relationship between SARS-CoV-2 and human reproduction may be very helpful in the long run in preventing and controlling COVID-19 and its aftermath.