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Human sperm displays rapid responses to diet.
PLOS Biology ( IF 7.8 ) Pub Date : 2019-12-26 , DOI: 10.1371/journal.pbio.3000559
Daniel Nätt 1 , Unn Kugelberg 1 , Eduard Casas 2 , Elizabeth Nedstrand 3 , Stefan Zalavary 3 , Pontus Henriksson 4, 5 , Carola Nijm 3 , Julia Jäderquist 3 , Johanna Sandborg 4, 5 , Eva Flinke 5 , Rashmi Ramesh 1 , Lovisa Örkenby 1 , Filip Appelkvist 1 , Thomas Lingg 1 , Nicola Guzzi 6 , Cristian Bellodi 6 , Marie Löf 4, 5 , Tanya Vavouri 2 , Anita Öst 1
Affiliation  

The global rise in obesity and steady decline in sperm quality are two alarming trends that have emerged during recent decades. In parallel, evidence from model organisms shows that paternal diet can affect offspring metabolic health in a process involving sperm tRNA-derived small RNA (tsRNA). Here, we report that human sperm are acutely sensitive to nutrient flux, both in terms of sperm motility and changes in sperm tsRNA. Over the course of a 2-week diet intervention, in which we first introduced a healthy diet followed by a diet rich in sugar, sperm motility increased and stabilized at high levels. Small RNA-seq on repeatedly sampled sperm from the same individuals revealed that tsRNAs were up-regulated by eating a high-sugar diet for just 1 week. Unsupervised clustering identified two independent pathways for the biogenesis of these tsRNAs: one involving a novel class of fragments with specific cleavage in the T-loop of mature nuclear tRNAs and the other exclusively involving mitochondrial tsRNAs. Mitochondrial involvement was further supported by a similar up-regulation of mitochondrial rRNA-derived small RNA (rsRNA). Notably, the changes in sugar-sensitive tsRNA were positively associated with simultaneous changes in sperm motility and negatively associated with obesity in an independent clinical cohort. This rapid response to a dietary intervention on tsRNA in human sperm is attuned with the paternal intergenerational metabolic responses found in model organisms. More importantly, our findings suggest shared diet-sensitive mechanisms between sperm motility and the biogenesis of tsRNA, which provide novel insights about the interplay between nutrition and male reproductive health.

中文翻译:

人类精子对饮食表现出快速反应。

全球肥胖率上升和精子质量稳步下降是近几十年来出现的两个令人震惊的趋势。与此同时,来自模型生物的证据表明,父亲的饮食可以影响后代的代谢健康,这一过程涉及精子 tRNA 衍生的小 RNA (tsRNA)。在这里,我们报告人类精子对营养通量非常敏感,无论是在精子活力还是精子 tsRNA 的变化方面。在为期两周的饮食干预过程中,我们首先引入健康饮食,然后引入富含糖的饮食,精子活力增加并稳定在高水平。对同一个体重复采集的精子进行的小 RNA 测序显示,仅仅 1 周的高糖饮食即可上调 tsRNA。无监督聚类确定了这些 tsRNA 生物发生的两条独立途径:一条涉及一类在成熟核 tRNA 的 T 环中具有特异性切割的新型片段,另一条专门涉及线粒体 tsRNA。线粒体 rRNA 衍生的小 RNA (rsRNA) 的类似上调进一步支持了线粒体参与。值得注意的是,在一个独立的临床队列中,糖敏感 tsRNA 的变化与精子活力的同时变化呈正相关,与肥胖呈负相关。这种对人类精子 tsRNA 饮食干预的快速反应与模型生物体中发现的父代代际代谢反应相一致。更重要的是,我们的研究结果表明精子活力和 tsRNA 生物发生之间存在共同的饮食敏感机制,这为营养与男性生殖健康之间的相互作用提供了新的见解。
更新日期:2019-12-27
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