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Thiamethoxam inhibits blastocyst expansion and hatching via reactive-oxygen species-induced G2 checkpoint activation in pigs.
Cellular Signalling ( IF 4.8 ) Pub Date : 2018-08-24 , DOI: 10.1016/j.cellsig.2018.08.014
Zheng-Wen Nie 1 , Ying-Jie Niu 1 , Wenjun Zhou 1 , Yong-Han Kim 1 , Kyung-Tae Shin 1 , Xiang-Shun Cui 1
Affiliation  

Thiamethoxam (TMX) is a neonicotinoid insecticide. It has specific high toxicity to insects. Residues of TMX have been detected in various crops. Early embryo quality is vital for fertility. Excessive production of reactive oxygen species (ROS) can override embryonic antioxidant defenses, producing oxidative stress that triggers apoptosis, necrosis, and/or permanent DNA damage responses in the early embryo. Comparative studies have indicated that TMX hepatotoxicity is significant in mammals in acute tests, but little is known about accumulated chronic toxicity in early embryonic development. Porcine embryos were obtained here by the parthenogenetic activation of meiosis II oocytes and cultured in the PZM-5 medium with or without TMX. These embryos were evaluated by various methods. The expansion and hatching of blastocysts treated with TMX decreased by 21.73% and 16.71%, respectively, as compared with controls. In an analysis of 5-bromo-2-deoxyuridine (BrdU) incorporation, the rate of cell proliferation was 44.33% lower as compared with expanded blastocysts of the control group. ROS and γH2AX levels were higher in the TMX group than in the control group. Real-time reverse-transcription polymerase chain reaction showed that Sod1 expression increased and the expression of Mnsod, Gpx1, Igta5, and Cox2 decreased. A CDK1 kinase assay revealed that maturation-promoting factor (MPF) activity diminished by 31.41% in expanding blastocysts. In conclusion, these results suggest that TMX inhibits blastocyst expansion and hatching by ROS-induced DNA damage checkpoint activation, which inhibits the activation of MPF and cell cycle progression in porcine blastocysts.

中文翻译:

噻虫嗪通过活性氧诱导猪的G2检查点活化来抑制胚泡的膨胀和孵化。

噻虫嗪(TMX)是一种新烟碱类杀虫剂。它对昆虫具有特定的高毒性。在各种农作物中都检测到了TMX的残留物。早期胚胎质量对于生育能力至关重要。过量产生活性氧(ROS)可能会超出胚胎的抗氧化剂防御能力,从而产生氧化应激,从而触发早期胚胎的细胞凋亡,坏死和/或永久性DNA损伤反应。比较研究表明,在急性试验中,TMX的肝毒性在哺乳动物中很重要,但对早期胚胎发育中累积的慢性毒性知之甚少。此处通过减数分裂II卵母细胞的孤雌性活化获得猪胚,并在有或没有TMX的PZM-5培养基中培养。通过各种方法评估这些胚胎。与对照组相比,TMX处理的胚泡的膨胀和孵化分别降低了21.73%和16.71%。在对5-溴-2-脱氧尿苷(BrdU)掺入的分析中,与对照组的膨胀胚泡相​​比,细胞增殖率低44.33%。TMX组的ROS和γH2AX水平高于对照组。实时逆转录聚合酶链反应显示Sod1表达增加,而Mnsod,Gpx1,Igta5和Cox2的表达减少。CDK1激酶测定显示,在膨胀的胚泡中,成熟促进因子(MPF)活性降低了31.41%。总之,这些结果表明TMX通过ROS诱导的DNA损伤检查点激活来抑制胚泡膨胀和孵化,
更新日期:2018-08-24
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