Back

Vitamin E supplementation prevents ferroptosis in round spermatids of aged mice

Germeraad, J.; Kikkawa, T.; Osumi, N.

2024-10-24 molecular biology
10.1101/2024.10.21.619554 bioRxiv
Show abstract

Age-related testicular germ cell depletion has been predominantly attributed to apoptosis; however, the contribution of alternative cell death modalities remains unclear. Using young and aged mice, we demonstrate compartment-specific cell-death signatures in the testis. Apoptotic cell increased in peripheral germ layers, whereas the luminal round spermatid (RS) layer mainly accumulated non-apoptotic events sharing features with ferroptosis, a lipid-peroxidation dependent cell death. Lipidomic analysis revealed age-related phospholipid remodelling in whole testis, while RS-enriched fractions showed increased lipid peroxidation. Interestingly, aging shifted the balance of sex-chromosome-bearing RS toward Y-bearing cells, and this bias persisted in mature sperm. Dietary vitamin E modulated these phenotypes bidirectionally: vitamin E deficiency in young mice increased RS lipid peroxidation and reproduced the Y-skew, whereas supplementation in aged mice lowered RS lipid peroxidation, decreased non-apoptotic events, and restored the skewed RS sex-chromosome ratio. These findings define an age-related RS vulnerability linking redox stress to haploid spermatogenic output.

Matching journals

The top 4 journals account for 50% of the predicted probability mass.

50% of probability mass above

"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.