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LncRNAs induce oxidative stress and spermatogenesis by regulating endoplasmic reticulum genes and pathways

Oligozoospermia or low sperm count is a leading cause of male infertility worldwide. Despite decades of work on non-coding RNAs (ncRNAs) as regulators of spermatogenesis, fertilization, and male fertility, the literature on the function of long non-coding RNAs (lncRNAs) in human oligozoospermia is s...

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Autores principales: Sun, Tie-Cheng, Zhang, Yi, Yu, Kun, Li, Yao, Yu, Hong, Zhou, Shan-Jie, Wang, Ya-Peng, Deng, Shou-Long, Tian, Li
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8202879/
https://www.ncbi.nlm.nih.gov/pubmed/34001678
http://dx.doi.org/10.18632/aging.202971
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author Sun, Tie-Cheng
Zhang, Yi
Yu, Kun
Li, Yao
Yu, Hong
Zhou, Shan-Jie
Wang, Ya-Peng
Deng, Shou-Long
Tian, Li
author_facet Sun, Tie-Cheng
Zhang, Yi
Yu, Kun
Li, Yao
Yu, Hong
Zhou, Shan-Jie
Wang, Ya-Peng
Deng, Shou-Long
Tian, Li
author_sort Sun, Tie-Cheng
collection PubMed
description Oligozoospermia or low sperm count is a leading cause of male infertility worldwide. Despite decades of work on non-coding RNAs (ncRNAs) as regulators of spermatogenesis, fertilization, and male fertility, the literature on the function of long non-coding RNAs (lncRNAs) in human oligozoospermia is scarce. We integrated lncRNA and mRNA sequencing data from 12 human normozoospermic and oligozoospermic samples and comprehensively analyzed the function of differentially expressed lncRNAs (DE lncRNAs) and mRNAs (DE mRNAs) in male infertility. The target genes of DE lncRNAs were identified using a Gaussian graphical model. Gene ontology terms and Kyoto Encyclopedia of Genes and Genomes pathways were primarily enriched in protein transport and localization to the endoplasmic reticulum (ER). The lncRNA–mRNA co-expression network revealed cis- and trans-regulated target genes of lncRNAs. The transcriptome data implicated DE lncRNAs and DE mRNAs and their target genes in the accumulation of unfolded proteins in sperm ER, PERK-EIF2 pathway-induced ER stress, oxidative stress, and sperm cell apoptosis in individuals with oligozoospermia. These findings suggest that the identified lncRNAs and pathways could serve as effective therapeutic targets for male infertility.
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spelling pubmed-82028792021-06-15 LncRNAs induce oxidative stress and spermatogenesis by regulating endoplasmic reticulum genes and pathways Sun, Tie-Cheng Zhang, Yi Yu, Kun Li, Yao Yu, Hong Zhou, Shan-Jie Wang, Ya-Peng Deng, Shou-Long Tian, Li Aging (Albany NY) Research Paper Oligozoospermia or low sperm count is a leading cause of male infertility worldwide. Despite decades of work on non-coding RNAs (ncRNAs) as regulators of spermatogenesis, fertilization, and male fertility, the literature on the function of long non-coding RNAs (lncRNAs) in human oligozoospermia is scarce. We integrated lncRNA and mRNA sequencing data from 12 human normozoospermic and oligozoospermic samples and comprehensively analyzed the function of differentially expressed lncRNAs (DE lncRNAs) and mRNAs (DE mRNAs) in male infertility. The target genes of DE lncRNAs were identified using a Gaussian graphical model. Gene ontology terms and Kyoto Encyclopedia of Genes and Genomes pathways were primarily enriched in protein transport and localization to the endoplasmic reticulum (ER). The lncRNA–mRNA co-expression network revealed cis- and trans-regulated target genes of lncRNAs. The transcriptome data implicated DE lncRNAs and DE mRNAs and their target genes in the accumulation of unfolded proteins in sperm ER, PERK-EIF2 pathway-induced ER stress, oxidative stress, and sperm cell apoptosis in individuals with oligozoospermia. These findings suggest that the identified lncRNAs and pathways could serve as effective therapeutic targets for male infertility. Impact Journals 2021-05-06 /pmc/articles/PMC8202879/ /pubmed/34001678 http://dx.doi.org/10.18632/aging.202971 Text en Copyright: © 2021 Sun et al. https://creativecommons.org/licenses/by/3.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/3.0/) (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Sun, Tie-Cheng
Zhang, Yi
Yu, Kun
Li, Yao
Yu, Hong
Zhou, Shan-Jie
Wang, Ya-Peng
Deng, Shou-Long
Tian, Li
LncRNAs induce oxidative stress and spermatogenesis by regulating endoplasmic reticulum genes and pathways
title LncRNAs induce oxidative stress and spermatogenesis by regulating endoplasmic reticulum genes and pathways
title_full LncRNAs induce oxidative stress and spermatogenesis by regulating endoplasmic reticulum genes and pathways
title_fullStr LncRNAs induce oxidative stress and spermatogenesis by regulating endoplasmic reticulum genes and pathways
title_full_unstemmed LncRNAs induce oxidative stress and spermatogenesis by regulating endoplasmic reticulum genes and pathways
title_short LncRNAs induce oxidative stress and spermatogenesis by regulating endoplasmic reticulum genes and pathways
title_sort lncrnas induce oxidative stress and spermatogenesis by regulating endoplasmic reticulum genes and pathways
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8202879/
https://www.ncbi.nlm.nih.gov/pubmed/34001678
http://dx.doi.org/10.18632/aging.202971
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