Xu Xiucai, He Liuyuan, Zhang Aimei, Li Qing, Hu Wen, Chen He, Du Jian, Shen Jilong
Anhui Provincial Laboratories of Pathogen Biology and Zoonoses, Department of Microbiology and Parasitology, Anhui Medical University, 81 Meishan Road, Hefei 230032, China; The Central Laboratory of Affiliated Provincial Hospital, Anhui Medical University, Hefei 230031, China.
Anhui Provincial Laboratories of Pathogen Biology and Zoonoses, Department of Microbiology and Parasitology, Anhui Medical University, 81 Meishan Road, Hefei 230032, China.
Exp Parasitol. 2015 Jul;154:51-61. doi: 10.1016/j.exppara.2015.04.008. Epub 2015 Apr 23.
Congenital toxoplasmosis may result in abortion, severe mental retardation and neurologic damage in the offspring. Placental damage is considered as the key event in this disease. Here we show that maternal infection with Toxoplasma gondii Wh3 isolate of genotype Chinese 1, which is predominantly prevalent in China, induced trophoblast apoptosis of pregnant mouse. PCR array analysis of 84 key genes in the biogenesis and functions of mouse mitochondrion revealed that ten genes were up-regulated at least 2-fold in the Wh3 infection group, compared with those in the control. The elevated levels of reactive oxygen species (ROS), malondialdehyde (MDA) and 8-hydroxydeoxyguanosine (8-OHdG), as well as the decreased glutathione (GSH), were observed in the infected mice. The mRNA levels of NADPH oxidase 1 and glutathione peroxidase 6 (GPx6) were significantly increased. The production of excessive ROS was NADPH oxidase-dependent, which contributed to mitochondrial structural damage and mitochondrial dysfunction in placentas, followed by the cleavage of caspase-9 and caspase-3, and finally resulted in apoptosis of trophoblasts. All the above-mentioned phenomena were inhibited by pretreatment with the antioxidant of N-acetylcysteine (NAC). Taken together, we concluded that Wh3 infection during pregnancy may contribute to trophoblast apoptosis by oxidative stress-induced mitochondrial dysfunction and activation of the downstream signaling pathway.
先天性弓形虫病可能导致后代流产、严重智力发育迟缓及神经损伤。胎盘损伤被认为是该疾病的关键事件。在此我们表明，孕期母体感染在中国主要流行的基因型为中国1型的弓形虫Wh3分离株，可诱导孕鼠滋养层细胞凋亡。对小鼠线粒体生物发生及功能中的84个关键基因进行PCR芯片分析发现，与对照组相比，Wh3感染组中有10个基因上调至少2倍。在感染小鼠中观察到活性氧（ROS）、丙二醛（MDA）和8-羟基脱氧鸟苷（8-OHdG）水平升高，以及谷胱甘肽（GSH）水平降低。NADPH氧化酶1和谷胱甘肽过氧化物酶6（GPx6）的mRNA水平显著升高。过量ROS的产生依赖于NADPH氧化酶，这导致胎盘线粒体结构损伤和线粒体功能障碍，随后半胱天冬酶-9和半胱天冬酶-3裂解，最终导致滋养层细胞凋亡。用N-乙酰半胱氨酸（NAC）抗氧化剂预处理可抑制上述所有现象。综上所述，我们得出结论，孕期Wh3感染可能通过氧化应激诱导的线粒体功能障碍和下游信号通路激活导致滋养层细胞凋亡。
