细颗粒物（PM2.5）是造成健康风险最重要的大气污染物，目前有关PM2.5对生殖损伤的影响已受到学界的关注，然而PM2.5致雄性生殖损伤机制尚不明确。我们预试验研究发现，PM2.5暴露的大鼠睾丸组织中出现内质网应激感应蛋白IRE1和自噬特异性蛋白Beclin1表达升高。另有研究报道，JNK是IRE1的下游信号分子，且可调控自噬的发生。据此我们提出假说，PM2.5可能通过激活IRE1-JNK-Beclin1信号通路介导大鼠睾丸损伤。为了验证这一假说，本课题拟以PM2.5暴露大鼠模型为研究对象，从观察不同周期及暴露剂量入手，分析IRE1、JNK及Beclin1在睾丸损伤过程中的变化。同时结合体外实验，采用药理学干预及RNA干扰技术对上述关联加以验证。以此综合评价PM2.5对睾丸损伤的影响及其与IRE1-JNK-Beclin1信号通路的关联，为寻找PM2.5致睾丸损伤新的治疗靶点提供线索和思路。

Fine particulate matter (PM2.5) is considered as the most significant air pollutant that contributes to health risks. At present, potential adverse effects of PM2.5 on reproductive injury have raised concerns. However, the pathogenesis of male reproductive injury underlying PM2.5 has not been well clarified. Our previous research found that PM2.5 had significantly increased the expression of endoplasmic reticulum stress-sensing protein IRE1 and autophagy-specific protein Beclin1 in rat testis. Other studies have shown that JNK was the downstream effector of IRE1 signaling, and which also was a potentially triggered autophagy regulation pathway as well. Accordingly, we hypothesized that whether PM2.5 -induced rat testicular injury by activating the IRE1-JNK-Beclin1 signaling pathway. In order to verify this hypothesis, PM2.5 rat model was used in this experiment. This study was to examine the changes of IRE1, JNK and Beclin1 in the process of testicular injury from the observation of different cycles and exposure dose. Combined with in vitro cell model by pharmacological intervention and RNA interference, the study will be performed to further investigate and discuss the above hypotheses. The study will comprehensively evaluate the effect of PM2.5 on testicular injury and its association with IRE1-JNK-Beclin1 signaling pathway, and thereby will provide clues and ideas for finding new therapeutic targets for PM2.5-induced testicular injury.