PM2.5 exposure induces reproductive injury through IRE1/JNK/autophagy signaling in male rats
PM2.5 exposure induces reproductive injury through IRE1/JNK/autophagy signaling in male rats
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PM2.5 暴露通过 IRE1/JNK/自噬信号诱导雄性大鼠生殖损伤
DOI：
10.1016/j.ecoenv.2021.111924
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发表时间：
2021
影响因子：
6.8
通讯作者：
李福琴
中科院分区：
文献类型：
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作者：
杨阳;冯亚静;黄辉;崔留欣;李福琴
细颗粒物（PM2.5）是造成健康风险的最重要的空气污染物。然而，PM2.5引起的雄性生殖损伤的机制尚未阐明。在本研究中，我们探讨是否PM2.5激活肌醇需要酶1（IRE 1）/c-Jun氨基末端激酶（JNK）/自噬信号通路，以及是否该通路介导雄性大鼠生殖损伤。建立PM2.5（1.5 mg/kg）致雄性SD大鼠生殖损伤模型，观察IRE 1抑制剂STF 083010（1 mg/kg）的干预作用。暴露4周后，分析生殖损伤相关指标和IRE 1-cascade蛋白表达。结果表明，PM2.5暴露后，精子质量和血清睾酮水平显著下降，凋亡指数增加。STF 083010干预后，精子质量和血清睾酮水平明显改善，凋亡指数降低。光镜下观察到PM2.5组生精细胞结构疏松，生精细胞和成熟精子数量减少。STF 083010干预后，对生精细胞的结构损伤得到改善，脱落细胞数量减少。Western blotting分析显示，在PM2.5组中，IRE 1、磷酸化JNK（p-JNK）、beclin-1和微管相关蛋白1轻链3（LC 3）II/LC 3 I蛋白的表达显著上调，而p62蛋白的表达显著下调。STF 083010的伴随施用显著地拮抗了上述副作用。STF 083010对暴露于PM2.5的雄性大鼠的生殖损伤相关效应具有特异性保护作用，其作用通过IRE 1/JNK/自噬信号转导介导。
Fine particulate matter (PM2.5) constitutes the most significant air pollutant that causes health risks. However, the mechanism(s) underlying PM2.5-induced male reproductive injury has not been clarified. In the present study we explored whether PM2.5 activated the inositol-requiring enzyme 1 (IRE1)/c-Jun NH 2-terminal kinase (JNK)/autophagy-signaling pathway, and whether this pathway mediated reproductive injury in male rats. We established a male Sprague–Dawley rat model of PM2.5 (1.5 mg/kg) exposure-induced reproductive injury, and observed the intervention effects of STF083010 (an IRE1 inhibitor, 1 mg/kg). After 4 weeks of exposure, reproductive injury-related indicators and IRE1-cascade protein expression were analyzed. Our results showed that sperm quality and serum testosterone level significantly decreased and apoptotic index increased after exposure to PM2.5. After STF083010 intervention, sperm quality and serum testosterone level were significantly improved, while the apoptotic index was reduced. Under light microscopy, we observed that the structure of spermatogenic cells in the PM2.5 group was loose, and that the numbers of spermatogenic cells and mature spermatozoa were reduced. After STF083010 intervention, the structural damage to spermatogenic cells was improved, and the number of cells shed was reduced. Western blotting analysis showed that the expression of IRE1, phosphorylated JNK (p-JNK), beclin-1, and microtubule-associated protein 1 light chain 3(LC3)II/LC3I proteins was significantly upregulated, and that the expression of p62 protein was significantly downregulated in the PM2.5 group. The concomitant administration of STF083010 significantly antagonized the aforementioned adverse effects. STF083010 exerted specific protective effects on reproductive injury-related effects in male rats exposed to PM2.5, with effects mediated via IRE1/JNK/autophagy signaling.