Gan Shiming, Zhou Shumin, Zhou Jiaming, Zhang Guanghui, Chen Jingshou, Liu Rui, Sun Kuan, Li Sisi, Xiong Wenjing, Wen Yujiao, Sheng Jianzhong, Zhang Yu, Ren Jingchao, Li Youjiang, Huang Hefeng, Zhang Chen
Department of Reproductive Medicine, Center for Reproductive Medicine, the Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine, Zhejiang University, Yiwu, 322000, China.
Department of Urology & Andrology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310029, China.
Adv Sci (Weinh). 2025 Oct;12(38):e05148. doi: 10.1002/advs.202505148. Epub 2025 Jul 25.
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.
环境微塑料的惊人流行率引发了全球对生育能力的关注。然而，聚四氟乙烯（PTFE，特氟龙）这种在不粘锅广泛使用的微塑料对精子质量的损害仍不明确。在此，报告了PTFE在男性生殖系统中的高检出率（46.62%）和生物蓄积情况，并在人类和小鼠中研究了PTFE暴露对男性生育能力的影响机制，同时探索了潜在的治疗策略。这些发现表明，PTFE暴露会延迟精原细胞和精母细胞的发育，破坏染色体联会和DNA损伤反应，并促进精母细胞的凋亡。有趣的是，PTFE暴露特异性地靶向单倍体精子细胞中的SKAP2，导致精子细胞骨架破坏、精子形态异常和精子活力下降。引人注目的是，针对SKAP2的治疗可重塑人类和小鼠的精子细胞骨架和形态，并恢复精子活力和男性生育能力。总的来说，这些研究阐明了PTFE暴露损害精子发生的机制，并突出了靶向SKAP2作为治疗人类弱畸精子症的一种有前景的治疗策略。
