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  3. Perfluorooctanoic acid alternatives hexafluoropropylene oxides exert male reproductive toxicity by disrupting blood-testis barrier

Perfluorooctanoic acid alternatives hexafluoropropylene oxides exert male reproductive toxicity by disrupting blood-testis barrier

  • Sci Total Environ. 2022 Nov 10;846:157313. doi: 10.1016/j.scitotenv.2022.157313.
Bi-Xia Peng 1,  Fangfang Li 2,  Monika Mortimer 3,  Xiang Xiao 4,  Ya Ni 5,  Yuyang Lei 6,  Minjie Li 7,  Liang-Hong Guo 8
Affiliations

Affiliations

  • 1 College of Life Sciences, China Jiliang University, Hangzhou, Zhejiang 310018, China; Institute of Environmental and Health Sciences, China Jiliang University, Hangzhou, Zhejiang 310018, China. Electronic address: s1909071023@cjlu.edu.cn.
  • 2 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. Electronic address: liff@cjlu.edu.cn.
  • 3 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. Electronic address: mmortimer@cjlu.edu.cn.
  • 4 Center for Reproductive Health, School of Pharmaceutical Sciences, Hangzhou Medical College, Zhejiang Academy of Medical Sciences, Hangzhou, Zhejiang 310063, China. Electronic address: xxiao@zjams.cn.
  • 5 Center for Reproductive Health, School of Pharmaceutical Sciences, Hangzhou Medical College, Zhejiang Academy of Medical Sciences, Hangzhou, Zhejiang 310063, China.
  • 6 College of Life Sciences, China Jiliang University, Hangzhou, Zhejiang 310018, China; Institute of Environmental and Health Sciences, China Jiliang University, Hangzhou, Zhejiang 310018, China. Electronic address: s1909071017@cjlu.edu.cn.
  • 7 College of Quality and Safety Engineering, China Jiliang University, Hangzhou, Zhejiang 310018, China. Electronic address: mjli@cjlu.edu.cn.
  • 8 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. Electronic address: lhguo@cjlu.edu.cn.
PMID: 35842142 DOI: 10.1016/j.scitotenv.2022.157313
Abstract

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.

Keywords

Blood-testis barrier; Hexafluoropropylene oxide; Male reproductive toxicity; Perfluorooctanoic acid; p38 MAPK.

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