Transcript Isoforms of SLC7A11-AS1 Are Associated With Varicocele-Related Male Infertility

Oxidative stress is one of the crucial mediators of varicocele-related male infertility. Recently, roles of long noncoding RNAs (lncRNAs) in oxidative stress have begun to emerge, however, little is known about their role in male infertility. The aim of this study was to determine the role of lncRNA SLC7A11-AS1 in varicocele-related male infertility. Through a high-throughput bioinformatics investigation, we predicted that lncRNA SLC7A11-AS1 might be involved in this type of infertility. The reactive oxygen species (ROS) levels and expression levels of SLC7A11-AS1 isoforms were evaluated in ejaculated spermatozoa of 25 infertile men with varicocele and 17 fertile individuals as control. Isoform 6 of SLC7A11-AS1 that showed a significant elevation in infertile men with varicocele relative to the fertile group was overexpressed in testicular-derived carcinoma cell lines (NT2 and NCCIT) followed by assessment of ROS, glutathione (GSH), lipid peroxidation, and cell viability. Overexpression of SLC7A11-AS1 isoform 6 in NT2 and NCCIT cell lines resulted in a significant downregulation of SLC7A11 gene expression, which consequently decreased GSH levels and concomitantly increased ROS levels and enhanced lipid peroxidation, which jeopardized cell survival and promoted cell death. Our finding revealed a potential role of oxidative-related lncRNAs in the pathophysiology of male infertility associated with varicocele.