Cohen-Krais, J. | bioRxiv Science

bioRxiv2024

Within-ejaculate haploid selection reduces disease biomarkers in human sperm

The germline is widely regarded as a checkpoint against the inheritance of damaged genomes, yet the mechanisms that could enact such filtering remain poorly resolved. Of the millions of sperm in a human ejaculate, only one fertilises the egg, creating a strong opportunity for selection among gametes. Combining within-ejaculate selection on sperm quality with whole-genome sequencing and proteomics in healthy donors, we find that this selection is biased against molecular signatures of age-related disease. The most reproducibly diverging genes are tumour suppressors, and genes diverging under sperm longevity-based selection are enriched for senescence-associated genes involved in genome maintenance and oxidative stress response. High-quality sperm are further depleted of inflammation- and cancer-associated proteins. This genomic signature is conserved in zebrafish, in which longer-lived sperm sire longer-lived offspring. We propose that within-ejaculate selection acts as a pre-fertilisation filter against age-related disease alleles, with implications for offspring lifespan and healthspan.

molecular biology↗

bioRxiv2024

Gum Arabic (Acacia senegal) enhances reproduction and modulates the microbiota-gut-brain axis of zebrafish in a sex-specific and dosage-dependent manner

Dietary fibres (DFs) constitute a wide range of heterogeneous compounds that resist digestion and have beneficial effects on general health. Gum Arabic (GA) is a tree exudate consisting of 90% arabinogalactan, a polymer of arabinose and galactose sugars with prebiotic properties. As a dietary fibre, GA improves renal function, metabolism, and immune response in humans and animals. However, the underlying mechanisms leading to these health benefits are poorly understood. We supplemented female and male zebrafish (Danio rerio) with two concentrations of GA (6% and 60%) for two weeks. We assessed the effects of GA supplementation on the gut microbiome composition, intestinal and brain metabolic profiles, reproductive fitness, and brain gene expression. We found that GA supplementation resulted in changes to the gut microbiome with a relative increase in Fusobacteria and a relative decrease in Proteobacteria where the beneficial genus Cetobacterium was significantly more abundant after supplementation. GA supplementation increased acetate levels, particularly in the brain, causing a decreased expression of cart1 in the brain of female zebrafish. While GA supplementation increased overall activity in male and female fish, reproductive fitness was negatively affected by GA supplementation in females. Our results suggest that while GA supplementation may have positive effects on metabolic rate and overall activity, it may come at a trade-off with reproductive fitness. Significance StatementDietary fibres, found in plant-based food sources, can improve health. They include natural gums like gum Arabic, a highly sought-after food additive used as a homogeniser. Despite our better understanding of nutrition, a fibre gap is still prevalent in the Western world with efforts being made to incorporate new sources to close this gap and boost well-being. Here, we showed that when gum Arabic was supplemented into the zebrafish diet, it had a beneficial modulatory effect on the microbiota-gut-brain axis and reproductive fitness. Our findings support the benefits of dietary fibres but also link their impact to sexual dimorphism and dosage. This has implications for developing nutrition guidelines for both animals and humans.

systems biology↗