Epididymal RNase T2 contributes to astheno-teratozoospermia and intergenerational metabolic disorder through epididymosome-sperm interaction.
Epididymal RNase T2 contributes to astheno-teratozoospermia and intergenerational metabolic disorder through epididymosome-sperm interaction.
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DOI：
10.1186/s12916-023-03158-1
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发表时间：
2023-11-22
期刊：
影响因子：
9.3
通讯作者：
Liu, Yue
中科院分区：
文献类型：
--
作者：
Ma, Zhuoyao;Li, Jinyu;Fu, Li;Fu, Rong;Tang, Ningyuan;Quan, Yanmei;Xin, Zhixiang;Ding, Zhide;Liu, Yue
关键词：
附睾对于睾丸后精子的发育是至关重要的，这被称为精子成熟。在这个过程中，受精能力是通过交换蛋白质和小的非编码RNA(SncRNAs)通过附精-精子通讯获得的。更重要的是，附睾上皮细胞分泌的附睾源外切体将SncRNA转移到成熟的精子中。这些单链RNA可以调节代际遗传，从而进一步影响后代的健康。近年来，精子成熟过程中SncRNAs与精子功能调控的联系和机制日益受到人们的关注。建立附睾特异性核糖核酸酶T2(RNaseT2)敲入(KI)小鼠模型，探讨其在精子受精能力发育中的作用。测定了RNaseT2KI雄鱼的精子参数，并对其后代的代谢表型进行了分析。Pandora测序技术对精子SncRNA的表达模式进行了分析和测序，以确定附睾部RNase T2对精子SncRNA表达水平的影响。此外，在体外和体内都证实了RNaseT2在附睾上皮细胞中的表达水平与环境应激的反应。RNaseT2基因的过表达导致小鼠附睾头弱精子症相关的严重不育，进而导致子代的获得性代谢紊乱，包括高血糖、高脂血症和高胰岛素血症。Pandora测序显示，与对照精子相比，RNaseT2 KI精子中的SncRNAs特别是rRNA衍生的小RNA(RsRNAs)和tRNA衍生的小RNAs(TsRNAs)的图谱发生了变化。此外，环境胁迫还上调了附睾头的核糖核酸酶T2。附睾核糖核酸酶T2在诱导精子成熟和代际遗传中的重要性得到了证实。附睾头核糖核酸酶T2的过度表达可导致子代弱畸形精子症和代谢紊乱。网上版载有补充材料，可在10.1186/s12916-023-03158-1查阅。
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. 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. 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. 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. The online version contains supplementary material available at 10.1186/s12916-023-03158-1.
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影响因子：
14.9
作者：
Chan PP;Lowe TM
通讯作者：
Lowe TM
DOI：
10.1074/jbc.ra118.005433
发表时间：
2018-12-21
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Huang J;Liu P;Wang G
通讯作者：
Wang G
影响因子：
7.7
作者：
Chan, JL;Blüher, S;Mantzoros, CS
通讯作者：
Mantzoros, CS
DOI：
10.1073/pnas.1222079110
发表时间：
2013-05-14
影响因子：
11.1
作者：
Acquati, Francesco;Lualdi, Marta;Taramelli, Roberto
通讯作者：
Taramelli, Roberto
影响因子：
13.3
作者：
Inhorn, Marcia C.;Patrizio, Pasquale
通讯作者：
Patrizio, Pasquale