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Epididymal RNase T2 contributes to astheno-teratozoospermia and intergenerational metabolic disorder through epididymosome-sperm interaction
BACKGROUND: The epididymis is crucial for post-testicular sperm development which is termed sperm maturation. During this process, fertilizing ability is acquired through the epididymis-sperm communication via exchange of protein and small non-coding RNAs (sncRNAs). More importantly, epididymal-deri...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10664275/ https://www.ncbi.nlm.nih.gov/pubmed/37993934 http://dx.doi.org/10.1186/s12916-023-03158-1 |
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author | Ma, Zhuoyao Li, Jinyu Fu, Li Fu, Rong Tang, Ningyuan Quan, Yanmei Xin, Zhixiang Ding, Zhide Liu, Yue |
author_facet | Ma, Zhuoyao Li, Jinyu Fu, Li Fu, Rong Tang, Ningyuan Quan, Yanmei Xin, Zhixiang Ding, Zhide Liu, Yue |
author_sort | Ma, Zhuoyao |
collection | PubMed |
description | BACKGROUND: The epididymis is crucial for post-testicular sperm development which is termed sperm maturation. During this process, fertilizing ability is acquired through the epididymis-sperm communication via exchange of protein and small non-coding RNAs (sncRNAs). More importantly, epididymal-derived exosomes secreted by the epididymal epithelial cells transfer sncRNAs into maturing sperm. These sncRNAs could mediate intergenerational inheritance which further influences the health of their offspring. Recently, the linkage and mechanism involved in regulating sperm function and sncRNAs during epididymal sperm maturation are increasingly gaining more and more attention. METHODS: An epididymal-specific ribonuclease T2 (RNase T2) knock-in (KI) mouse model was constructed to investigate its role in developing sperm fertilizing capability. The sperm parameters of RNase T2 KI males were evaluated and the metabolic phenotypes of their offspring were characterized. Pandora sequencing technology profiled and sequenced the sperm sncRNA expression pattern to determine the effect of epididymal RNase T2 on the expression levels of sperm sncRNAs. Furthermore, the expression levels of RNase T2 in the epididymal epithelial cells in response to environmental stress were confirmed both in vitro and in vivo. RESULTS: Overexpression of RNase T2 caused severe subfertility associated with astheno-teratozoospermia in mice caput epididymis, and furthermore contributed to the acquired metabolic disorders in the offspring, including hyperglycemia, hyperlipidemia, and hyperinsulinemia. Pandora sequencing showed altered profiles of sncRNAs especially rRNA-derived small RNAs (rsRNAs) and tRNA-derived small RNAs (tsRNAs) in RNase T2 KI sperm compared to control sperm. Moreover, environmental stress upregulated RNase T2 in the caput epididymis. CONCLUSIONS: The importance was demonstrated of epididymal RNase T2 in inducing sperm maturation and intergenerational inheritance. Overexpressed RNase T2 in the caput epididymis leads to astheno-teratozoospermia and metabolic disorder in the offspring. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12916-023-03158-1. |
format | Online Article Text |
id | pubmed-10664275 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-106642752023-11-22 Epididymal RNase T2 contributes to astheno-teratozoospermia and intergenerational metabolic disorder through epididymosome-sperm interaction Ma, Zhuoyao Li, Jinyu Fu, Li Fu, Rong Tang, Ningyuan Quan, Yanmei Xin, Zhixiang Ding, Zhide Liu, Yue BMC Med Research Article BACKGROUND: The epididymis is crucial for post-testicular sperm development which is termed sperm maturation. During this process, fertilizing ability is acquired through the epididymis-sperm communication via exchange of protein and small non-coding RNAs (sncRNAs). More importantly, epididymal-derived exosomes secreted by the epididymal epithelial cells transfer sncRNAs into maturing sperm. These sncRNAs could mediate intergenerational inheritance which further influences the health of their offspring. Recently, the linkage and mechanism involved in regulating sperm function and sncRNAs during epididymal sperm maturation are increasingly gaining more and more attention. METHODS: An epididymal-specific ribonuclease T2 (RNase T2) knock-in (KI) mouse model was constructed to investigate its role in developing sperm fertilizing capability. The sperm parameters of RNase T2 KI males were evaluated and the metabolic phenotypes of their offspring were characterized. Pandora sequencing technology profiled and sequenced the sperm sncRNA expression pattern to determine the effect of epididymal RNase T2 on the expression levels of sperm sncRNAs. Furthermore, the expression levels of RNase T2 in the epididymal epithelial cells in response to environmental stress were confirmed both in vitro and in vivo. RESULTS: Overexpression of RNase T2 caused severe subfertility associated with astheno-teratozoospermia in mice caput epididymis, and furthermore contributed to the acquired metabolic disorders in the offspring, including hyperglycemia, hyperlipidemia, and hyperinsulinemia. Pandora sequencing showed altered profiles of sncRNAs especially rRNA-derived small RNAs (rsRNAs) and tRNA-derived small RNAs (tsRNAs) in RNase T2 KI sperm compared to control sperm. Moreover, environmental stress upregulated RNase T2 in the caput epididymis. CONCLUSIONS: The importance was demonstrated of epididymal RNase T2 in inducing sperm maturation and intergenerational inheritance. Overexpressed RNase T2 in the caput epididymis leads to astheno-teratozoospermia and metabolic disorder in the offspring. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12916-023-03158-1. BioMed Central 2023-11-22 /pmc/articles/PMC10664275/ /pubmed/37993934 http://dx.doi.org/10.1186/s12916-023-03158-1 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Article Ma, Zhuoyao Li, Jinyu Fu, Li Fu, Rong Tang, Ningyuan Quan, Yanmei Xin, Zhixiang Ding, Zhide Liu, Yue Epididymal RNase T2 contributes to astheno-teratozoospermia and intergenerational metabolic disorder through epididymosome-sperm interaction |
title | Epididymal RNase T2 contributes to astheno-teratozoospermia and intergenerational metabolic disorder through epididymosome-sperm interaction |
title_full | Epididymal RNase T2 contributes to astheno-teratozoospermia and intergenerational metabolic disorder through epididymosome-sperm interaction |
title_fullStr | Epididymal RNase T2 contributes to astheno-teratozoospermia and intergenerational metabolic disorder through epididymosome-sperm interaction |
title_full_unstemmed | Epididymal RNase T2 contributes to astheno-teratozoospermia and intergenerational metabolic disorder through epididymosome-sperm interaction |
title_short | Epididymal RNase T2 contributes to astheno-teratozoospermia and intergenerational metabolic disorder through epididymosome-sperm interaction |
title_sort | epididymal rnase t2 contributes to astheno-teratozoospermia and intergenerational metabolic disorder through epididymosome-sperm interaction |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10664275/ https://www.ncbi.nlm.nih.gov/pubmed/37993934 http://dx.doi.org/10.1186/s12916-023-03158-1 |
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