Ovarian Dysfunction Induced by Chronic Whole-Body PM2.5 Exposure
Ovarian Dysfunction Induced by Chronic Whole-Body PM2.5 Exposure
复制标题
全身长期接触 PM2.5 诱发卵巢功能障碍
DOI：
10.1002/smll.202000845
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发表时间：
2020-07-19
期刊：
影响因子：
13.3
通讯作者：
Wang, Shixuan
中科院分区：
文献类型：
--
作者：
Zhou, Su;Xi, Yueyue;Wang, Shixuan
细颗粒物（PM2.5）污染引起了全球范围内的公共卫生关注。越来越多的流行病学证据表明，暴露于空气中的PM2.5会增加女性不孕的风险。然而，相对较少的研究系统地探讨了慢性PM2.5暴露对卵巢功能的有害影响及其潜在机制。在这项研究中，雌性C57 BL/6 J小鼠通过全身暴露系统暴露于过滤空气或城市空气中的PM2.5 4个月。研究发现，PM2.5暴露显著改变了发情周期、生殖能力、激素水平和卵巢储备功能。颗粒细胞凋亡通过线粒体依赖途径参与卵泡闭锁。RNA测序结果显示，PM2.5暴露诱导的差异表达基因主要集中在卵巢类固醇生成、活性氧和氧化磷酸化途径。此外，研究发现，增加的PM2.5通过NF-κ B/IL-6信号通路严重加剧了小鼠卵巢氧化应激和炎症。值得注意的是，膳食白藜芦醇苷（PD）补充剂对小鼠对抗PM2.5诱导的卵巢功能障碍具有保护作用。这些引人注目的发现表明，PM2.5和/或空气污染是通过线粒体依赖性和NF-κ B/IL-6介导的途径导致卵巢功能障碍的关键因素，PD可能成为治疗空气污染相关卵巢功能障碍的候选药物。
Fine particulate matter (PM2.5) pollution arouses public health concerns over the world. Increasing epidemiologic evidence suggests that exposure to ambient airborne PM2.5 increases the risk of female infertility. However, relatively few studies have systematically explored the harmful effect of chronic PM2.5 exposure on ovarian function and the underlying mechanisms. In this study, female C57BL/6J mice are exposed to filtered air or urban airborne PM2.5 for 4 months through a whole-body exposure system. It is found that PM2.5 exposure significantly caused the alteration of estrus cycles, reproductivity, hormone levels, and ovarian reserve. The granulosa cell apoptosis via the mitochondria dependent pathway contributes to the follicle atresia. With RNA-sequencing technique, the differentially expressed genes induced by PM2.5 exposure are mainly enriched in ovarian steroidogenesis, reactive oxygen species and oxidative phosphorylation pathways. Furthermore, it is found that increased PM2.5 profoundly exacerbated ovarian oxidative stress and inflammation in mice through the NF-kappa B/IL-6 signaling pathway. Notably, dietary polydatin (PD) supplement has protective effect in mice against PM2.5-induced ovarian dysfunction.These striking findings demonstrate that PM2.5 and/or air pollution is a critical factor for ovarian dysfunction through mitochondria-dependent and NF-kappa B/IL-6-mediated pathway, and PD may serve as a pharmaceutic candidate for air pollution-associated ovarian dysfunction.