Our previous study revealed a higher incidence of gene dynamic mutation in newborns conceived by IVF, highlighting that IVF may be disruptive to the DNA stability of IVF offspring. However, the underlying mechanisms remain unclear. The DNA damage repair system plays an essential role in gene dynamic mutation and neurodegenerative disease. To evaluate the long-term impact of IVF on DNA damage repair genes, we established an IVF mouse model and analyzed gene and protein expression levels of MSH2, MSH3, MSH6, MLH1, PMS2, OGG1, APEX1, XPA and RPA1 and also the amount of H2AX phosphorylation of serine 139 which is highly suggestive of DNA double-strand break (γH2AX expression level) in the brain tissue of IVF conceived mice and their DNA methylation status using quantitative real-time PCR, western blotting and pyrosequencing. Furthermore, we assessed the capacity of two specific non-physiological factors in IVF procedures during preimplantation development. The results demonstrated that the expression and methylation levels of some DNA damage repair genes in the brain tissue of IVF mice were significantly changed at 3 weeks, 10 weeks and 1.5 years of age, when compared with the in vivo control group. In support of mouse model findings, oxygen concentration of in vitro culture environment was shown to have the capacity to modulate gene expression and DNA methylation levels of some DNA damage repair genes. In summary, our study indicated that IVF could bring about long-term alterations of gene and protein expression and DNA methylation levels of some DNA damage repair genes in the brain tissue and these alterations might be resulted from the different oxygen concentration of culture environment, providing valuable perspectives to improve the safety and efficiency of IVF at early embryonic stage and also throughout different life stages.

中文翻译：

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DNA损伤修复基因在体外受精小鼠脑组织中的表达改变。

我们先前的研究揭示了IVF怀胎的新生儿基因动态突变的发生率更高，表明IVF可能破坏IVF后代的DNA稳定性。但是，其潜在机制仍不清楚。DNA损伤修复系统在基​​因动态突变和神经退行性疾病中起着至关重要的作用。为了评估IVF对DNA损伤修复基因的长期影响，我们建立了IVF小鼠模型，并分析了MSH2，MSH3，MSH6，MLH1，PMS2，OGG1，APEX1，XPA和RPA1的基因和蛋白质表达水平，以及其数量实时荧光定量PCR，Western印迹和焦磷酸测序技术提示IVF怀胎小鼠脑组织中H2AX磷酸丝氨酸139的磷酸化，高度暗示了其DNA双链断裂（γH2AX表达水平）及其DNA甲基化状态。此外，我们评估了植入前发育过程中试管婴儿手术中两个特定的非生理因素的能力。结果表明，与体内对照组相比，IVF小鼠脑组织中某些DNA损伤修复基因的表达和甲基化水平在3周，10周和1.5岁时发生了显着变化。为了支持小鼠模型的发现，体外培养环境中的氧气浓度显示具有调节某些DNA损伤修复基因的基因表达和DNA甲基化水平的能力。综上所述，