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

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 sequen...

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Autores principales: Kyrgiafini, Maria-Anna, Giannoulis, Themistoklis, Chatziparasidou, Alexia, Christoforidis, Nikolaos, Mamuris, Zissis
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10573971/
https://www.ncbi.nlm.nih.gov/pubmed/37834450
http://dx.doi.org/10.3390/ijms241915002
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author Kyrgiafini, Maria-Anna
Giannoulis, Themistoklis
Chatziparasidou, Alexia
Christoforidis, Nikolaos
Mamuris, Zissis
author_facet Kyrgiafini, Maria-Anna
Giannoulis, Themistoklis
Chatziparasidou, Alexia
Christoforidis, Nikolaos
Mamuris, Zissis
author_sort Kyrgiafini, Maria-Anna
collection PubMed
description 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.
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spelling pubmed-105739712023-10-14 Unveiling the Genetic Complexity of Teratozoospermia: Integrated Genomic Analysis Reveals Novel Insights into lncRNAs’ Role in Male Infertility Kyrgiafini, Maria-Anna Giannoulis, Themistoklis Chatziparasidou, Alexia Christoforidis, Nikolaos Mamuris, Zissis Int J Mol Sci Article 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. MDPI 2023-10-09 /pmc/articles/PMC10573971/ /pubmed/37834450 http://dx.doi.org/10.3390/ijms241915002 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Kyrgiafini, Maria-Anna
Giannoulis, Themistoklis
Chatziparasidou, Alexia
Christoforidis, Nikolaos
Mamuris, Zissis
Unveiling the Genetic Complexity of Teratozoospermia: Integrated Genomic Analysis Reveals Novel Insights into lncRNAs’ Role in Male Infertility
title Unveiling the Genetic Complexity of Teratozoospermia: Integrated Genomic Analysis Reveals Novel Insights into lncRNAs’ Role in Male Infertility
title_full Unveiling the Genetic Complexity of Teratozoospermia: Integrated Genomic Analysis Reveals Novel Insights into lncRNAs’ Role in Male Infertility
title_fullStr Unveiling the Genetic Complexity of Teratozoospermia: Integrated Genomic Analysis Reveals Novel Insights into lncRNAs’ Role in Male Infertility
title_full_unstemmed Unveiling the Genetic Complexity of Teratozoospermia: Integrated Genomic Analysis Reveals Novel Insights into lncRNAs’ Role in Male Infertility
title_short Unveiling the Genetic Complexity of Teratozoospermia: Integrated Genomic Analysis Reveals Novel Insights into lncRNAs’ Role in Male Infertility
title_sort unveiling the genetic complexity of teratozoospermia: integrated genomic analysis reveals novel insights into lncrnas’ role in male infertility
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10573971/
https://www.ncbi.nlm.nih.gov/pubmed/37834450
http://dx.doi.org/10.3390/ijms241915002
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