Obesity impairs spermatogenesis via Leydig cell ferroptosis induced by liver-derived exosomal miR-122-5p.

ABSTRACT: Obesity increases the risk of male infertility, primarily attributable to reduced testosterone levels. Exosomes, which facilitate intercellular communication during reproduction, may influence this process. However, the relation between exosomal cargo changes and high-fat diet (HFD)-induced testosterone decrease remains unclear. Here, we show that exosomes influence testosterone synthesis and spermatogenesis in HFD mice. Transferring exosomes derived from the serum of HFD mice to mice fed a normal diet decreases testosterone levels and sperm counts. Treatment with inhibitors of exosomes (GW4869) and ferroptosis (Ferrostatin-1) rescue HFD-induced impaired spermatogenesis. Additionally, elevated miR-122-5p levels in serum exosomes from HFD mice is partially attributed to increased hepatic mi

SUBMITTER: Wang N 

PROVIDER: S-EPMC12936086 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature