Ferroptotic vulnerability of post-meiotic germ cells skews sex chromosome ratios in aged testis
Abstract
Germ cell depletion in the aged testes has traditionally been attributed to removal by apoptosis. This study aimed to determine whether ferroptosis, an alternative form of cell death driven by iron dependent lipid peroxidation, also contributes to germ cell loss in the lipid rich environment of the testis. Here, we demonstrate that pre-meiotic cells are eliminated via apoptosis, whereas post-meiotic round spermatids (RSs) are mainly removed through ferroptosis. Surprisingly, we detected a greater abundance of Y chromosome bearing RSs (Y RSs) than X-carrying RSs (X RSs) in the aged testis, implying that X RSs might be more prone to ferroptosis. Young mice fed a vitamin E (VE) deficient diet recapitulated age-related phenotypes, while VE supplementation prevented ferroptosis and promoted the survival of X RSs in aged mice. Overall, this study reveals that aging causes ferroptosis in RSs, specifically impacting X RSs, which can be prevented by VE supplementation, effectively reversing age induced deterioration and contributing to healthy testicular aging.
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Research summary
The study claims that post-meiotic round spermatids are primarily removed through ferroptosis, particularly affecting X chromosome-bearing cells, and that vitamin E supplementation can prevent this process. This research addresses a mechanism of cell death in the context of aging, contributing to our understanding of age-related changes in germ cell viability and potential interventions to promote healthier aging in the testis.
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