Zang Xupeng, Wang Yongzhong, Jiang Lei, Qiu Yuhao, Ding Yue, Gu Shengchen, Cai Gengyuan, Gu Ting, Hong Linjun
State Key Laboratory of Swine and Poultry Breeding Industry, National Engineering Research Center for Breeding Swine Industry, Guangdong Provincial Key Laboratory of Agro-Animal Genomics and Molecular Breeding, College of Animal Science, South China Agricultural University, Guangzhou, 510642, China.
Yunfu Subcenter of Guangdong Laboratory for Lingnan Modern Agriculture, Yunfu, 527300, China.
J Anim Sci Biotechnol. 2025 Mar 11;16(1):42. doi: 10.1186/s40104-025-01177-x.
Hexafluoropropylene oxide dimer acid (GenX), a substitute for per- and polyfluoroalkyl substances, has been widely detected in various environmental matrices and foods recently, attracting great attention. However, a systematic characterization of its reproductive toxicity is still missing. This study aims to explore the male reproductive toxicity caused by GenX exposure and the potential cellular and molecular regulatory mechanisms behind it.
Normally developing mice were exposed to GenX, and testicular tissue was subsequently analyzed and validated using single-cell RNA sequencing. Our results revealed that GenX induced severe testicular damage, disrupted the balance between undifferentiated and differentiated spermatogonial stem cells, and led to strong variation in the cellular dynamics of spermatogenesis. Furthermore, GenX exposure caused global upregulation of testicular somatic cellular inflammatory responses, increased abnormal macrophage differentiation, and attenuated fibroblast adhesion, disorganizing the somatic-germline interactions.
In conclusion, this study revealed complex cellular dynamics and transcriptome changes in mouse testis after GenX exposure, providing a valuable resource for understanding its reproductive toxicity.
六氟环氧丙烷二聚酸（GenX）作为全氟和多氟烷基物质的替代品，近年来在各种环境基质和食品中被广泛检测到，引起了广泛关注。然而，其生殖毒性的系统表征仍然缺失。本研究旨在探讨GenX暴露引起的雄性生殖毒性及其潜在的细胞和分子调控机制。
将正常发育的小鼠暴露于GenX，随后使用单细胞RNA测序对睾丸组织进行分析和验证。我们的结果表明，GenX诱导严重的睾丸损伤，破坏未分化和分化的精原干细胞之间的平衡，并导致精子发生细胞动力学的强烈变化。此外，GenX暴露导致睾丸体细胞炎症反应的整体上调，增加异常巨噬细胞分化，并减弱成纤维细胞粘附，破坏体细胞与生殖细胞之间的相互作用。
总之，本研究揭示了GenX暴露后小鼠睾丸复杂的细胞动力学和转录组变化，为理解其生殖毒性提供了有价值的资源。
