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Article

Unveiling the Genetic Complexity of Teratozoospermia: Integrated Genomic Analysis Reveals Novel Insights into lncRNAs’ Role in Male Infertility

by
Maria-Anna Kyrgiafini
1,
Themistoklis Giannoulis
2,
Alexia Chatziparasidou
3,
Nikolaos Christoforidis
3 and
Zissis Mamuris
1,*
1
Laboratory of Genetics, Comparative and Evolutionary Biology, Department of Biochemistry and Biotechnology, University of Thessaly, Viopolis, Mezourlo, 41500 Larissa, Greece
2
Laboratory of Biology, Genetics and Bioinformatics, Department of Animal Sciences, University of Thessaly, Gaiopolis, 41336 Larissa, Greece
3
Embryolab IVF Unit, St. 173-175 Ethnikis Antistaseos, Kalamaria, 55134 Thessaloniki, Greece
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2023, 24(19), 15002; https://doi.org/10.3390/ijms241915002
Submission received: 26 August 2023 / Revised: 3 October 2023 / Accepted: 4 October 2023 / Published: 9 October 2023
(This article belongs to the Special Issue Molecular Approaches to Male Infertility: From Diagnosis to Decision-Making)
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Abstract

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: male infertility; teratozoospermia; long-noncoding RNA (lncRNA); variant male infertility; teratozoospermia; long-noncoding RNA (lncRNA); variant

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MDPI and ACS Style

Kyrgiafini, M.-A.; Giannoulis, T.; Chatziparasidou, A.; Christoforidis, N.; Mamuris, Z. Unveiling the Genetic Complexity of Teratozoospermia: Integrated Genomic Analysis Reveals Novel Insights into lncRNAs’ Role in Male Infertility. Int. J. Mol. Sci. 2023, 24, 15002. https://doi.org/10.3390/ijms241915002

AMA Style

Kyrgiafini M-A, Giannoulis T, Chatziparasidou A, Christoforidis N, Mamuris Z. Unveiling the Genetic Complexity of Teratozoospermia: Integrated Genomic Analysis Reveals Novel Insights into lncRNAs’ Role in Male Infertility. International Journal of Molecular Sciences. 2023; 24(19):15002. https://doi.org/10.3390/ijms241915002

Chicago/Turabian Style

Kyrgiafini, Maria-Anna, Themistoklis Giannoulis, Alexia Chatziparasidou, Nikolaos Christoforidis, and Zissis Mamuris. 2023. "Unveiling the Genetic Complexity of Teratozoospermia: Integrated Genomic Analysis Reveals Novel Insights into lncRNAs’ Role in Male Infertility" International Journal of Molecular Sciences 24, no. 19: 15002. https://doi.org/10.3390/ijms241915002

APA Style

Kyrgiafini, M.-A., Giannoulis, T., Chatziparasidou, A., Christoforidis, N., & Mamuris, Z. (2023). Unveiling the Genetic Complexity of Teratozoospermia: Integrated Genomic Analysis Reveals Novel Insights into lncRNAs’ Role in Male Infertility. International Journal of Molecular Sciences, 24(19), 15002. https://doi.org/10.3390/ijms241915002

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