Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China.
Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, China.
Front Immunol. 2021 Dec 1;12:734546. doi: 10.3389/fimmu.2021.734546. eCollection 2021.
As an important source of air pollutant, airborne particulate matter (PM) has become a major threat to public health. Orchitis is characterized by acute or chronic testicular inflammation and is a primary cause of male infertility. Although accumulating evidence indicates that PM exposure is associated with increased male infertility rates, the mechanism by which PM is involved is not well understood. Here, we found that short-term PM exposure activated NF-κB signaling in mouse Leydig cells and testes and leading to asymptomatic orchitis. Analyzing the mitochondrial abundance and cGAMP levels in PM exposed mouse Leydig cells, we found that PM exposure induced mitochondrial injury and mtDNA release, leading to inflammation the cGAS-STING axis. We also found that aspirin-induced acetylation of cGAS inhibited the inflammation in mice after PM exposure, especially in the testes. Moreover, aspirin pretreatment rescued offspring growth in PM-exposed mice. In summary, our study not only provides evidence that PM-induced asymptomatic orchitis in mice may be amenable to aspirin pre-treatment by acetylating cGAS, but also provides a potential explanation for male infertility caused by air pollutants.
作为空气污染物的重要来源，空气中的颗粒物（PM）已成为公众健康的主要威胁。睾丸炎的特征为急性或慢性睾丸炎症，是男性不育的主要原因。尽管越来越多的证据表明 PM 暴露与男性不育率的增加有关，但 PM 参与的机制尚不清楚。在这里，我们发现短期 PM 暴露会激活小鼠 Leydig 细胞和睾丸中的 NF-κB 信号通路，导致无症状睾丸炎。分析 PM 暴露的小鼠 Leydig 细胞中的线粒体丰度和 cGAMP 水平，我们发现 PM 暴露会导致线粒体损伤和 mtDNA 释放，从而引发炎症反应通过 cGAS-STING 轴。我们还发现，阿司匹林诱导的 cGAS 乙酰化可抑制 PM 暴露后小鼠的炎症反应，尤其是在睾丸中。此外，阿司匹林预处理可挽救 PM 暴露小鼠的后代生长。总之，我们的研究不仅为 PM 诱导的小鼠无症状睾丸炎可能通过乙酰化 cGAS 进行阿司匹林预处理提供了证据，还为空气污染引起的男性不育提供了潜在的解释。
