Apoptosis and blood-testis barrier disruption during male reproductive dysfunction induced by PAHs of different molecular weights

细胞凋亡 粘合连接 生殖毒性 支持细胞 氧化应激 分子生物学 化学 苯并(a)芘 微核试验 流式细胞术 男科 标记法 荧蒽 毒性 生物 精子发生 生物化学 内分泌学 细胞 致癌物 医学 环境化学 有机化学 钙粘蛋白
作者
Lin Zhang,Xiaoli Ji,Hang Fan,Xuan Wu,Ning Tang,Qing Wu
出处
期刊:Environmental Pollution [Elsevier BV]
卷期号:300: 118959-118959 被引量:24
标识
DOI:10.1016/j.envpol.2022.118959
摘要

The association between polycyclic aromatic hydrocarbons (PAHs) and male reproductive dysfunction has attracted increasing attention. The purpose of this study was to compare the male reproductive toxicity of multiple PAHs and to investigate the underlying molecular mechanisms. TM4 cells (mouse testicular Sertoli cells, SCs) were treated with benzo(a)pyrene (BaP), pyrene (Py), fluoranthene (Fl) and phenanthrene (Phe) (0, 0.1, 1, 10, 50, or 100 μM) for varying time points (4, 12, 24, or 48 h), and male C57BL/6 mice were administered BaP and Py (0, 10, 50, or 100 mg/kg body weight) for 14 days based on the cell experimental results. Histopathological examination, western blotting, ELISA, biochemical assays, RT-PCR, flow cytometry, JC-1 staining and trans-epithelium electrical resistance (TEER) measurements were used to assess apoptosis, blood-testis barrier (BTB) integrity, intracellular calcium ([Ca2+]i) concentrations and oxidative stress (OS). The results revealed that the mRNA levels and enzymatic activities of CYP450 and GST family members; levels of ROS, MDA, cleaved caspase 3 (c-caspase 3), caspase 9, Bax, and cytochrome C (CytC); and numbers of TUNEL-positive cells were significantly increased by BaP and Py, while levels of AhR, GSH, SOD, CAT, Bcl-2 and ΔΨm were decreased. Additionally, BaP and Py notably interfered with tight junctions (TJs) and adherens junctions (AJs) in the BTB. Intriguingly, BaP, but not Py, induced [Ca2+]i overload and gap junction (GJ) destruction. There was no dramatic effect of Fl and/or Phe on any of the above parameters except that slight cytotoxicity was observed with higher doses of Fl. Collectively, these findings showed that BaP and Py elicited SC apoptosis and BTB disruption involving mitochondrial dysfunction and OS, but [Ca2+]i fluctuation and GJ injury were only observed with BaP-induced reproductive toxicity. The male reproductive toxicity of the selected PAHs was ranked in the order of BaP > Py > Fl > Phe.
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