Male infertility is a global health issue, affecting over 20 million men worldwide. Genetic factors are crucial in various male infertility forms, including teratozoospermia. Nonetheless, the genetic causes of male infertility remain largely unexplored. In this study, we employed whole-genome sequencing and RNA expression analysis to detect differentially expressed (DE) long-noncoding RNAs (lncRNAs) in teratozoospermia, along with mutations that are exclusive to teratozoospermic individuals within these DE lncRNAs regions. Bioinformatic tools were used to assess variants' impact on lncRNA structure, function, and lncRNA-miRNA interactions. Our analysis identified 1166 unique mutations in teratozoospermic men within DE lncRNAs, distinguishing them from normozoospermic men. Among these, 64 variants in 23 lncRNAs showed potential regulatory roles, 7 variants affected 4 lncRNA structures, while 37 variants in 17 lncRNAs caused miRNA target loss or gain. Pathway Enrichment and Gene Ontology analyses of the genes targeted by the affected miRNAs revealed dysregulated pathways in teratozoospermia and a link between male infertility and cancer. This study lists novel variants and lncRNAs associated for the first time with teratozoospermia. These findings pave the way for future studies aiming to enhance diagnosis and therapy in the field of male infertility.
Keywords: long-noncoding RNA (lncRNA); male infertility; teratozoospermia; variant.