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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...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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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. |
format | Online Article Text |
id | pubmed-10573971 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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