Toxoplasma gondii isolate with genotype Chinese 1 triggers trophoblast apoptosis through oxidative stress and mitochondrial dysfunction in mice.
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.
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. Electronic address: xuxiucai1972@163.com.
Xiucai
X
Xu
Anhui Provincial Laboratories of Pathogen Biology and Zoonoses, Department of Microbiology and Parasitology, Anhui Medical University, 81 Meishan Road, Hefei 230032, China.
Liuyuan
L
He
The Central Laboratory of Affiliated Provincial Hospital, Anhui Medical University, Hefei 230031, China.
Aimei
A
Zhang
The Central Laboratory of Affiliated Provincial Hospital, Anhui Medical University, Hefei 230031, China.
Qing
Q
Li
Department of Pathology of Affiliated Provincial Hospital, Anhui Medical University, Hefei, China.
Wen
W
Hu
Anhui Provincial Laboratories of Pathogen Biology and Zoonoses, Department of Microbiology and Parasitology, Anhui Medical University, 81 Meishan Road, Hefei 230032, China.
He
H
Chen
Department of Biochemistry and Molecular Biology, Anhui Medical University, Hefei 230032, China.
Jian
J
Du
Anhui Provincial Laboratories of Pathogen Biology and Zoonoses, Department of Microbiology and Parasitology, Anhui Medical University, 81 Meishan Road, Hefei 230032, China. Electronic address: shenjilong53@126.com.
Jilong
J
Shen
D000818:Animals; D017209:Apoptosis; D005260:Female; D005838:Genotype; D008297:Male; D008564:Membrane Potentials; D051379:Mice; D008807:Mice, Inbred BALB C; D008928:Mitochondria / Q000473:pathology / Q000502:physiology; D018384:Oxidative Stress; D010920:Placenta / Q000378:metabolism / Q000503:physiopathology; D011247:Pregnancy; D015597:Pregnancy Complications, Parasitic / Q000378:metabolism / Q000469:parasitology / Q000473:pathology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D014122:Toxoplasma / Q000145:classification / Q000235:genetics / Q000502:physiology*; D014124:Toxoplasmosis, Animal / Q000378:metabolism / Q000469:parasitology / Q000473:pathology*; D059467:Transcriptome; D014327:Trophoblasts / Q000473:pathology*
D017382:Reactive Oxygen Species
Apoptosis; Mitochondrial dysfunction; Oxidative stress; Toxoplasma gondii