Human sperm displays rapid responses to diet

Abstract

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 tRNAderived 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 sugarsensitive 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.

Histone Post-Translational Modifications and CircRNAs in Mouse and Human Spermatozoa: Potential Epigenetic Marks to Assess Human Sperm Quality

“…, outlines the main functions of sperm RNA types in spermatogenesis and SPZ). [78] rsRNAs Mature SPZ are enriched in rsRNAs [50] rsRNAs are considered sperm quality biomarkers [49] Small RNA profiles in ejaculated sperm, epididymal sperm and seminal plasma indicate that sperm RNAs may have origins other than the testes [79] The deletion of a mouse tRNA methyltransferase, DNMT2, abolisheds sperm sncRNA-mediated transmission of high-fat diet (HFD)-induced metabolic disorders to offspring [80] Since SPZ are transcriptionally and translationally silent cells before departing the testes [81], it is plausible that the substantial remodeling of their ncRNA cargo may be driven extrinsically along the epididymis, a long convoluted tubule connecting rete testis to the vas deferens, composed of three main anatomical regions (caput, corpus and cauda), with a considerable segment to segment variation. Leading candidates to promote this crosstalk are epididymal epithelial cells that communicate with SPZ through epididymosomes, vesicles-heterogeneous in their lipid/protein/RNA composition and density-released through an apocrine secretory mechanism [82].…”

Novel insights into the emerging roles of tRNA-derived fragments in mammalian development

“…This study further revealed that Dnmt2-mediated m 5 C affected the secondary structure and biological properties of abundant 3ʹ-tRFs upon transfection in cell lines [46], although the exact contribution of m 5 C for tRF-mediated paternal inheritance was not fully delineated. Similarly, a recent study in humans showed that i-tRF levels in sperm cells from healthy donors were dynamically modulated in response to acute diet intervention and were positively associated with increased sperm motility [48]. Hence, further studies will be required to qualitatively assess the function of tRFs during the early developmental stages and their contribution to the transmission of paternally acquired metabolic traits.…”

tRNA-Derived Small RNAs and Their Potential Roles in Cardiac Hypertrophy

“…Therefore, the study raised a very intriguing question of whether tsRNAs induced by cardiac hypertrophy could be inherited by the next generation and lead to pathogenesis. In fact, there are several lines of evidence consistently indicating that tsRNAs are enriched in sperm (Chen et al, 2016;Sharma et al, 2016;Natt et al, 2019;Sarker et al, 2019;Zhang et al, 2019). Some studies demonstrated the intergenerational inheritance of tsRNAs by injecting tsRNAs from the sperm of males fed a high fat diet into normal zygotes, and showed the offspring had altered expression of metabolic pathway components in addition to developing a metabolic disorder (Chen et al, 2016;Sarker et al, 2019).…”