Human sperm displays rapid responses to diet

Area of Science:

• Reproductive Biology
• Epigenetics
• Nutritional Science

Background:

• Global trends show rising obesity and declining sperm quality.
• Paternal diet influences offspring metabolic health via sperm tRNA-derived small RNAs (tsRNAs) in model organisms.

Purpose of the Study:

• Investigate the acute effects of nutrient flux on human sperm motility and tsRNA.
• Explore the relationship between diet, sperm tsRNA, and male reproductive health.

Main Methods:

• Conducted a 2-week diet intervention (healthy diet followed by high-sugar diet).
• Analyzed sperm motility and performed small RNA sequencing on sperm from the same individuals over time.
• Utilized unsupervised clustering to identify tsRNA biogenesis pathways.
• Examined associations in an independent clinical cohort.

Main Results:

• Human sperm motility increased and stabilized with a healthy diet, then further improved with a high-sugar diet.
• A high-sugar diet for 1 week upregulated sperm tsRNAs.
• Identified two tsRNA biogenesis pathways: one involving nuclear tRNAs and another involving mitochondrial tsRNAs.
• Observed positive association between sugar-sensitive tsRNAs and sperm motility, and negative association with obesity.

Conclusions:

• Human sperm are acutely sensitive to dietary changes, affecting both motility and tsRNA profiles.
• Dietary interventions rapidly alter sperm tsRNA, with distinct nuclear and mitochondrial pathways.
• Findings suggest shared diet-sensitive mechanisms linking nutrition, sperm function, and intergenerational metabolic health.