胎盘炎症是纳米材料导致胎儿发育异常的重要因素。研究证实，线粒体碎片化能激活线粒体自噬，而自噬体堆积可导致炎症发生。前期研究发现，孕期暴露纳米氧化锌（ZnO NPs）诱发胎盘炎症，滋养层细胞线粒体出现碎片化，但碎片化发生的具体调控机制尚不明确。申请人预实验发现，ZnO NPs可导致胞质中Ca2+水平显著升高，钙敏感传感器Miro活性减弱，线粒体出现碎片化，伴随线粒体自噬相关蛋白表达升高，炎症因子释放增多；下调胞质Ca2+浓度后，线粒体碎片化程度减弱，同时自噬水平降低。因此提出科学假说：ZnO NPs通过Ca2+/Miro通路导致线粒体碎片化，进而引起线粒体自噬异常堆积，诱导胎盘炎症。本课题拟采用基因敲除及免疫共沉淀等技术手段，对ZnO NPs诱导的胎盘炎症进行机制研究，以阐明Ca2+/Miro通路介导的线粒体碎片化在其中的调控作用。本课题的顺利进行为纳米材料孕期暴露的生物安全性提供参考依据。

Placental inflammation is an important factor of abnormal fetal development caused by nanomaterials. Studies have confirmed that mitochondrial fragmentation can activate mitochondrial autophagy, and autophagosome accumulation can lead to inflammation. Previous studies have found that exposure to nano zinc oxide (ZnO NPs) during pregnancy can induce placental inflammation, meanwhile mitochondria fragmentation of trophoblastic cell have happened, but the specific regulatory mechanism of mitochondria fragmentation is still unclear. Preliminary experiments found that ZnO NPs can lead to significantly increasement of Ca2+ level in cytoplasm, and decrease the activity of calcium-sensitive sensor Miro. Meanwhile, fragmentation of mitochondria had happened, it also increased the expression of mitochondrial autophagy related proteins as well as th inflammatory factors. After the concentration of cytoplasmic Ca2+ was down-regulated, the degree of mitochondrial fragmentation was weakened and the level of autophagy was reduced. Therefore, a scientific hypothesis is proposed: ZnO NPs leads to mitochondrial fragmentation through the Ca2+/Miro pathway, which leads to abnormal accumulation of mitochondrial autophagy and induces placental inflammation. This project intends to study the mechanism of ZnO NPs-induced placental inflammation by means of gene knockout and immunoprecipitation, so as to elucidate the regulatory role of Ca2+/Miro pathway mediated mitochondrial fragmentation. The success of this project provides a reference for the biosafety of nanomaterials during pregnancy.