Shaanxi Stem Cell Engineering and Technology Research Center, College of Veterinary Medicine, Northwest A&F University, Yangling 712100, China.
Key Laboratory of Infection and Immunity of Shandong Province, Department of Immunology, School of Biomedical Sciences, Shandong University, Jinan 250012, China.
Int J Mol Sci. 2020 Nov 24;21(23):8892. doi: 10.3390/ijms21238892.
As a common injury almost all cells face, DNA damage in oocytes-especially double-strand breaks (DSBs), which occur naturally during the first meiosis phase (meiosis I) due to synaptic complex separation-affects the fertilization ability of oocytes, instead of causing cancer (as in somatic cells). The mechanism of oocytes to effectively repair DSB damage has not yet been clearly studied, especially considering medically induced DSBs superimposed on naturally occurring DSBs in meiosis I. It was found that maturation rates decreased or increased, respectively corresponding with overexpression or interference of in bovine oocytes. At the same time, the maturation rate of bovine oocytes decreased with a gradual increase in Zeocin dose, and the expression in those immature oocytes changed significantly with the gradual increase in Zeocin dose (same as increased DSB intensity). Same as , the variation trend of expression was consistent with the gradual increase in Zeocin dose. Furthermore, the oocytes demonstrated tolerance to DSBs during meiosis I, while the maturation rates decreased when the damage exceeded a certain threshold; according to which, it may be that regulates the p53-p21 pathway to affect the completion of meiosis. In addition, nonhomologous recombination and cumulus cells are potentially involved in the process by which oocytes respond to DSB damage.
作为一种几乎所有细胞都会面临的常见损伤,卵母细胞中的 DNA 损伤——尤其是双链断裂(DSBs),由于突触复合体的分离,在第一次减数分裂阶段(减数分裂 I)中自然发生——会影响卵母细胞的受精能力,而不会像体细胞那样导致癌症。卵母细胞有效修复 DSB 损伤的机制尚未得到明确研究,尤其是考虑到医学诱导的 DSB 与减数分裂 I 中自然发生的 DSB 叠加在一起的情况。研究发现,在牛卵母细胞中,分别过表达或干扰 ,其成熟率会降低或增加。同时,随着 Zeocin 剂量的逐渐增加,牛卵母细胞的成熟率降低,这些未成熟卵母细胞中的 表达也随着 Zeocin 剂量的逐渐增加而显著变化(与 DSB 强度的增加相同)。与 相同, 的表达变化趋势与 Zeocin 剂量的逐渐增加一致。此外,卵母细胞在减数分裂 I 期间对 DSB 具有耐受性,而当损伤超过一定阈值时,成熟率会降低;据此,可能是 通过调节 p53-p21 通路来影响减数分裂的完成。此外,非同源重组和卵丘细胞可能参与了卵母细胞对 DSB 损伤的反应过程。