Abstract
Coronavirus disease 2019 (COVID-19), a global pandemic, is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Angiotensin-converting enzyme 2 (ACE2) is the receptor for SARS-CoV-2 and transmembrane serine protease 2 (TMPRSS2) facilitates ACE2-mediated virus entry. Moreover, the expression of ACE2 in the testes of infertile men is higher than normal, which indicates that infertile men may be susceptible to be infected and SARS-CoV-2 may cause reproductive disorder through the pathway induced by ACE2 and TMPRSS2. Little is known about the pathway regulation of ACE2 and TMPRSS2 expression in male reproductive disorder. Since the regulation of gene expression is mediated by microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) at the post-transcriptional level, the aim of this study was to analyze the dysregulated miRNA–lncRNA interactions of ACE2 and TMPRSS2 in male reproductive disorder. Using bioinformatics analysis, we speculate that the predicted miRNAs including miR-125a-5p, miR-125b-5p, miR-574-5p, and miR-936 as regulators of ACE2 and miR-204-5p as a modulator of TMPRSS2 are associated with male infertility. The lncRNAs with a tissue-specific expression for testis including GRM7-AS3, ARHGAP26-AS1, BSN-AS1, KRBOX1-AS1, CACNA1C-IT3, AC012361.1, FGF14-IT1, AC012494.1, and GS1-24F4.2 were predicted. The identified miRNAs and lncRNAs are proposed as potential biomarkers to study the possible association between COVID-19 and male infertility. This study encourages further studies of miRNA–lncRNA interactions to explain the molecular mechanisms of male infertility in COVID-19 patients.
Highlights
We identified the interactions between these miRNAs and differentially expressed long non-coding RNAs (lncRNAs) in infertile men identified by Joshi and Lu [32,33]
We explored the miRNAs that regulate angiotensin-converting enzyme 2 (ACE2) and TMPRSS2 and are associated with male infertility according to the study of Abu et al [30]
KRBOX1 was found to be over-expressed in testis by a previous study, its role has not been investigated [56]. As these lncRNAs were found to be differentially expressed in infertile men and their expression in healthy men was testis-specific, we proposed these lncRNAs as biomarkers that could explain the association between COVID-19 and male reproductive disorder
Summary
In December 2019, a novel coronavirus responsible for coronavirus disease 2019. (COVID-19) was described in Wuhan, China [1,2]. Nearly 146,000,000 global confirmed cases of COVID-19, with nearly 3 million deaths, have been observed [3]. SARS-CoV-2, a single-stranded RNA virus belonging to the coronavirus subfamily, is one of the seven different coronaviruses that can infect humans and is the pathogen responsible for COVID-19 [4]. 229E, NL63, OC43, and HKU1, can lead to mild viral symptoms, while the other three, SARS-CoV-1, MERS-CoV, and SARS-CoV-2, can cause more severe respiratory symptoms [4]. The angiotensin-converting enzyme 2 (ACE2) receptor and transmembrane serine protease 2 (TMPRSS2), localized on the host cell membrane, are indispensable for viral proliferation in the infected host [5]
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