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Overexpression of lncRNA-Gm2044 in spermatogonia impairs spermatogenesis in partial seminiferous tubules

Long noncoding RNAs (lncRNAs) have been demonstrated to regulate reproduction in mammals. Our previous study revealed that the expression level of lncRNA-Gm2044 was obviously elevated in nonobstructive azoospermia with spermatogonial arrest. Here, a transgenic mouse model of lncRNA-Gm2044 in spermat...

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Autores principales: Hu, Ke, Gao, Yuanyuan, Xu, Yifan, He, Chaofan, Wang, Kaixian, Li, Leina, Liao, Yaping, Liu, Xiaohua, Liang, Meng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9192819/
https://www.ncbi.nlm.nih.gov/pubmed/35691049
http://dx.doi.org/10.1016/j.psj.2022.101930
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author Hu, Ke
Gao, Yuanyuan
Xu, Yifan
He, Chaofan
Wang, Kaixian
Li, Leina
Liao, Yaping
Liu, Xiaohua
Liang, Meng
author_facet Hu, Ke
Gao, Yuanyuan
Xu, Yifan
He, Chaofan
Wang, Kaixian
Li, Leina
Liao, Yaping
Liu, Xiaohua
Liang, Meng
author_sort Hu, Ke
collection PubMed
description Long noncoding RNAs (lncRNAs) have been demonstrated to regulate reproduction in mammals. Our previous study revealed that the expression level of lncRNA-Gm2044 was obviously elevated in nonobstructive azoospermia with spermatogonial arrest. Here, a transgenic mouse model of lncRNA-Gm2044 in spermatogonia using the Stra8 promoter was constructed to explore the roles of upregulated lncRNA-Gm2044 in male fertility. Testicular morphology and fertility weren't affected in transgenic mice expressing lncRNA-Gm2044. However, overexpression of lncRNA-Gm2044 in spermatogonia partially impaired spermatogenesis in the transgenic mice. Then, transcriptome sequencing was executed to find the potential signaling pathway repressing spermatogenesis in germ cells of lncRNA-Gm2044 transgenic mice. Through quantitative analysis of differentially expressed genes, 442 upregulated mRNAs and 147 downregulated mRNAs were displayed in male germ cells of Gm2044-transgenic mice (Gm2044-Tg) compared with non-transgenic mice (Non-Tg). Using gene ontology (GO) analysis, differentially expressed genes were shown to play vital roles in RNA_metabolic_process, Central_element, Enzyme_binding, and Intracellular_bridge. Using Kyoto encyclopedia of genes and genomes (KEGG) analysis, differentially expressed genes were shown to participate in RNA_transport, Cell_cycle, Renin-angiotensin_system, and Chemokine_signaling_pathway. Gene Set Enrichment Analysis (GSEA) revealed that Acrosome_assembly and Sperm_plasma_membrane were involved in the overexpression of lncRNA-Gm2044 blocking spermatogenesis. Furthermore, some of the most differentially expressed mRNAs were verified by RT-qPCR. In addition, we determined that the lncRNA-Gm2044 has no ability to translate into peptides by the bioinformatics method and molecular experiment. Thus, lncRNA-Gm2044 is a novel molecular target for the diagnosis and treatment of male infertility.
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spelling pubmed-91928192022-06-15 Overexpression of lncRNA-Gm2044 in spermatogonia impairs spermatogenesis in partial seminiferous tubules Hu, Ke Gao, Yuanyuan Xu, Yifan He, Chaofan Wang, Kaixian Li, Leina Liao, Yaping Liu, Xiaohua Liang, Meng Poult Sci PHYSIOLOGY AND REPRODUCTION Long noncoding RNAs (lncRNAs) have been demonstrated to regulate reproduction in mammals. Our previous study revealed that the expression level of lncRNA-Gm2044 was obviously elevated in nonobstructive azoospermia with spermatogonial arrest. Here, a transgenic mouse model of lncRNA-Gm2044 in spermatogonia using the Stra8 promoter was constructed to explore the roles of upregulated lncRNA-Gm2044 in male fertility. Testicular morphology and fertility weren't affected in transgenic mice expressing lncRNA-Gm2044. However, overexpression of lncRNA-Gm2044 in spermatogonia partially impaired spermatogenesis in the transgenic mice. Then, transcriptome sequencing was executed to find the potential signaling pathway repressing spermatogenesis in germ cells of lncRNA-Gm2044 transgenic mice. Through quantitative analysis of differentially expressed genes, 442 upregulated mRNAs and 147 downregulated mRNAs were displayed in male germ cells of Gm2044-transgenic mice (Gm2044-Tg) compared with non-transgenic mice (Non-Tg). Using gene ontology (GO) analysis, differentially expressed genes were shown to play vital roles in RNA_metabolic_process, Central_element, Enzyme_binding, and Intracellular_bridge. Using Kyoto encyclopedia of genes and genomes (KEGG) analysis, differentially expressed genes were shown to participate in RNA_transport, Cell_cycle, Renin-angiotensin_system, and Chemokine_signaling_pathway. Gene Set Enrichment Analysis (GSEA) revealed that Acrosome_assembly and Sperm_plasma_membrane were involved in the overexpression of lncRNA-Gm2044 blocking spermatogenesis. Furthermore, some of the most differentially expressed mRNAs were verified by RT-qPCR. In addition, we determined that the lncRNA-Gm2044 has no ability to translate into peptides by the bioinformatics method and molecular experiment. Thus, lncRNA-Gm2044 is a novel molecular target for the diagnosis and treatment of male infertility. Elsevier 2022-04-27 /pmc/articles/PMC9192819/ /pubmed/35691049 http://dx.doi.org/10.1016/j.psj.2022.101930 Text en © 2022 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle PHYSIOLOGY AND REPRODUCTION
Hu, Ke
Gao, Yuanyuan
Xu, Yifan
He, Chaofan
Wang, Kaixian
Li, Leina
Liao, Yaping
Liu, Xiaohua
Liang, Meng
Overexpression of lncRNA-Gm2044 in spermatogonia impairs spermatogenesis in partial seminiferous tubules
title Overexpression of lncRNA-Gm2044 in spermatogonia impairs spermatogenesis in partial seminiferous tubules
title_full Overexpression of lncRNA-Gm2044 in spermatogonia impairs spermatogenesis in partial seminiferous tubules
title_fullStr Overexpression of lncRNA-Gm2044 in spermatogonia impairs spermatogenesis in partial seminiferous tubules
title_full_unstemmed Overexpression of lncRNA-Gm2044 in spermatogonia impairs spermatogenesis in partial seminiferous tubules
title_short Overexpression of lncRNA-Gm2044 in spermatogonia impairs spermatogenesis in partial seminiferous tubules
title_sort overexpression of lncrna-gm2044 in spermatogonia impairs spermatogenesis in partial seminiferous tubules
topic PHYSIOLOGY AND REPRODUCTION
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9192819/
https://www.ncbi.nlm.nih.gov/pubmed/35691049
http://dx.doi.org/10.1016/j.psj.2022.101930
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