Introduction: Angiotensin-converting enzyme II (ACE2) is the main receptor for severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) to enter the host cells. The higher expression of ACE2 receptor in the testis makes it more susceptible to SARS-COV-2 infection. Recent studies have reported orchitis, impaired spermatogenesis, and presence of viruses in semen of affected men. The main objective of this study is to understand the molecular alterations induced by SARS-CoV-2 and signaling pathways dysregulated in testis.
Methods: A data mining approach was employed to identify the RNA sequencing data of human testis infected with SARS-CoV-2. The FASTQ files (PRJNA661970) were retrieved from European Nucleotide Archive (ENA) for both the infected and control groups (non-infected). RNA seq data were further processed and analyzed, using BioJupies to generate a list of differentially expressed genes (DEGs). In addition, downstream analysis was carried out, using ingenuity pathway analysis software (Qiagen, USA) to identify the differentially regulated pathways and unique non-directional gene networks.
Results: A total of 17,824 genes were identified in the testis of both SARS CoV-2 infected and control groups, of which 4,131 genes were differentially expressed (2,492 downregulated and 1,639 upregulated) with a fold change cut-off of ±2 and P<0.05. Bioinformatic analysis revealed that molecular pathways, such as inflammatory response, reproductive system development and function, and cell-to-cell signaling and interaction, were dysregulated in testes of men infected with SARS-CoV-2. Furthermore, we have also identified enrichment of 37 DEGs in the germ cell-Sertoli cell junction signaling pathway (Table 1).
Conclusions: Our bioinformatic results clearly indicate that homeostasis of germ cell-Sertoli cell junction is disturbed during SARS-CoV-2 infection, which could be a predisposing cause for impaired spermatogenesis. Future studies are warranted to understand the impact of mild, moderate, and severe SARS-CoV-2 infections on germ cell-Sertoli cell junction in both vaccinated and unvaccinated populations that may affect their reproductive performance and fertility.