Therapeutic Repair of Sperm Quality Decline Caused by Polytetrafluoroethylene

Abstract The alarming prevalence of environmental microplastics has raised global concerns about fertility. However, the detriment of polytetrafluoroethylene (PTFE, Teflon), a widely used microplastic in non‐stick cookware, to sperm quality remains unclear. Here, a high detection rate (46.62%) and bioaccumulation of PTFE in the male urogenital system are reported and the mechanisms of PTFE exposure on male fertility are investigated in both humans and mice and potential therapeutic strategies are explored. These findings reveal that PTFE exposure delays the development of spermatogonia and spermatocytes, disrupts chromosomal synapsis and the DNA damage response, and promotes the apoptosis of spermatocytes. Interestingly, PTFE exposure specifically targets SKAP2 in the haploid spermatid, leading to disruption of the sperm cytoskeleton, abnormal sperm morphology, and decreased sperm motility. Strikingly, therapy targeting SKAP2 remodels sperm cytoskeleton and morphology and restores sperm motility and male fertility in humans and mice. Collectively, these works illustrate the mechanisms of PTFE exposure impairing spermatogenesis and highlight SKAP2 targeting as a promising therapeutic strategy for treating asthenoteratozoospermia in humans.