College of Life Sciences, China Jiliang University, Hangzhou, Zhejiang 310018, China; Institute of Environmental and Health Sciences, China Jiliang University, Hangzhou, Zhejiang 310018, China.
Institute of Environmental and Health Sciences, China Jiliang University, Hangzhou, Zhejiang 310018, China; College of Quality and Safety Engineering, China Jiliang University, Hangzhou, Zhejiang 310018, China.
Sci Total Environ. 2022 Nov 10;846:157313. doi: 10.1016/j.scitotenv.2022.157313. Epub 2022 Jul 14.
As alternatives to perfluorooctanoic acid (PFOA), hexafluoropropylene oxide (HFPO) homologues, including hexafluoropropylene oxide dimer acid (HFPO-DA), hexafluoropropylene oxide trimer acid (HFPO-TA), and hexafluoropropylene oxide tetramer acid (HFPO-TeA), have attracted widespread attention recently due to their environmental ubiquity and high potential for bioaccumulation and toxicity. In the present study, a set of in vivo mouse and in vitro mouse testicular Sertoli TM4 cell experiments were employed to explore the male reproductive toxicity and underlying mechanisms of HFPO homologues on blood-testis barrier. Tissue and permeability analyses of mice testes after 28-day treatment with 5 mg/kg/day HFPO-DA or PFOA, or 0.05 mg/kg/day HFPO-TA or HFPO-TeA indicated that there was an increase in the degradation of TJ protein occludin in mice with a disrupted blood-testis barrier (BTB). Following exposure to 100 μM HFPO-DA, HFPO-TA or 10 μM PFOA, HFPO-TeA, transepithelial electrical resistance measurements of TM4 cells also indicated BTB disruption. Additionally, as a result of the exposure, matrix metalloproteinase-9 expression was enhanced through activation of p38 MAPK, which promoted the degradation of occludin. On the whole, the results indicated HFPO homologues and PFOA induced BTB disruption through upregulation of p-p38/p38 MAPK/MMP-9 pathway, which promoted the degradation of TJ protein occludin and caused the disruption of TJ.
作为全氟辛酸 (PFOA) 的替代品，六氟环氧丙烷 (HFPO) 同系物，包括六氟环氧丙烷二聚酸 (HFPO-DA)、六氟环氧丙烷三聚酸 (HFPO-TA) 和六氟环氧丙烷四聚酸 (HFPO-TeA)，由于其在环境中的普遍存在以及高生物蓄积性和毒性潜力，最近引起了广泛关注。本研究采用体内小鼠和体外小鼠睾丸 TM4 细胞实验，探讨 HFPO 同系物对血睾屏障的雄性生殖毒性及其潜在机制。用 5mg/kg/d HFPO-DA 或 PFOA，或 0.05mg/kg/d HFPO-TA 或 HFPO-TeA 处理 28 天后，小鼠睾丸组织和通透性分析表明，TJ 蛋白紧密连接蛋白 occludin 降解增加，血睾屏障 (BTB) 受损。在 100μM HFPO-DA、HFPO-TA 或 10μM PFOA、HFPO-TeA 暴露后，TM4 细胞的跨上皮电阻测量也表明 BTB 破坏。此外，由于暴露，基质金属蛋白酶-9 的表达通过激活 p38 MAPK 增强，从而促进 occludin 的降解。总的来说，这些结果表明 HFPO 同系物和 PFOA 通过上调 p-p38/p38 MAPK/MMP-9 通路诱导 BTB 破坏，促进 TJ 蛋白紧密连接蛋白 occludin 的降解，导致 TJ 破坏。
