Aurora B prevents aneuploidy via MAD2 during the first mitotic cleavage in oxidatively damaged embryos
Aurora B prevents aneuploidy via MAD2 during the first mitotic cleavage in oxidatively damaged embryos
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Aurora B 在氧化损伤胚胎的第一次有丝分裂期间通过 MAD2 防止非整倍体
DOI：
10.1111/cpr.12657
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发表时间：
2019-07-01
影响因子：
8.5
通讯作者：
Xiao, Wanfen
中科院分区：
文献类型：
--
作者：
Li, Jiena;Ha, Siyao;Xiao, Wanfen
目的体外受精（IVF）胚胎染色体非整倍体发生率高。我们以前的实验表明，活性氧（ROS）可以激活Mad 2，纺锤体组装检查点（SAC）中的关键蛋白，并延迟第一次有丝分裂，为防止胚胎非整倍体的形成提供时间。我们的目的是确定有丝分裂激酶Aurora B是否参与SAC功能，以防止IVF衍生胚胎的非整倍体。材料与方法通过4-MODIFIER LETTER PRIME、6-diamidino-2-phenylindole（DAPI）染色和染色体核型分析，分析胚胎植入前非整倍体的形成和修复。我们通过免疫荧光评估Aurora B激活，并研究Aurora B抑制对胚胎损伤相关变量的影响，如胚胎发育、ROS水平、线粒体膜电位和γ H2 AX阳性表达。结果在氧化应激诱导的受精卵中，Aurora B中Thr 232的表达及磷酸化水平均明显升高。此外，抑制Aurora B可导致IVF胚胎染色体错误分离、纺锤体结构异常、染色体数目异常和Mad 2表达降低。我们的研究结果表明，极光B导致有丝分裂停滞，并通过Mad 2和H3 S10 P参与SAC，这是非整倍体自我校正所必需的。结论我们在这里证明，氧化应激诱导的DNA损伤触发Aurora B介导的SAC激活，从而防止在早期小鼠IVF胚胎的第一次有丝分裂分裂的非整倍体。
Objectives A high rate of chromosome aneuploidy is exhibited in in vitro fertilization (IVF)-derived embryos. Our previous experiments suggested that reactive oxygen species (ROS) can activate Mad2, a key protein in the spindle assembly checkpoint (SAC), and delay the first mitotic, providing time to prevent the formation of embryonic aneuploidy. We aimed to determine whether mitotic kinase Aurora B was involved in the SAC function to prevent aneuploidy in IVF-derived embryos. Materials and Methods We analysed aneuploidy formation and repair during embryo pre-implantation via 4MODIFIER LETTER PRIME,6-diamidino-2-phenylindole (DAPI) staining and karyotype analysis. We assessed Aurora B activation by immunofluorescence and investigated the effect of Aurora B inhibition on embryo injury-related variables, such as embryonic development, ROS levels, mitochondrial membrane potential and gamma H2AX-positive expression. Results We observed the expression and phosphorylation of Thr232 in Aurora B in oxidative stress-induced zygotes. Moreover, inhibition of Aurora B caused chromosome mis-segregation, abnormal spindle structures, abnormal chromosome number and reduced expression of Mad2 in IVF embryos. Our results suggest that Aurora B causes mitotic arrest and participates in SAC via Mad2 and H3S10P, which is required for self-correction of aneuploidies. Conclusions We demonstrate here that oxidative stress-induced DNA damage triggers Aurora B-mediated activation of SAC, which prevents aneuploidy at the first mitotic cleavage in early mouse IVF embryos.