单细胞转录组分析表明母体肥胖影响小鼠胚胎的 DNA 修复、组蛋白甲基化和自噬水平,Journal of Cellular Physiology

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单细胞转录组分析表明母体肥胖影响小鼠胚胎的 DNA 修复、组蛋白甲基化和自噬水平
Journal of Cellular Physiology ( IF 4.5 ) Pub Date : 2020-12-23 , DOI: 10.1002/jcp.30201
Meng-Hao Pan _{1,

2} , Cheng-Cheng Zhu ₂ , Jia-Qian Ju ₂ , Yi Xu ₂ , Shi-Ming Luo ₁ , Shao-Chen Sun ₂ , Xiang-Hong Ou ₁

Affiliation

肥胖会导致许多生殖功能障碍，如受孕减少、不孕和早孕，这主要是由于肥胖对卵母细胞和胚胎质量的负面影响。在本研究中，我们采用单细胞 RNA 转录组测序来研究母体肥胖对小鼠胚胎影响的潜在原因。我们的结果表明，在肥胖小鼠的胚胎发育过程中，4 细胞和桑椹胚/胚泡率均显着降低。全基因组分析表明，肥胖改变了 2 细胞胚胎中 1100 多个基因的表达，包括与 p53 信号通路和细胞凋亡相关的基因。进一步分析表明，47个与DNA损伤相关的基因表达发生了改变，γH2A信号呈阳性，而在肥胖胚胎中观察到Rad51和Tex15。肥胖也会影响组蛋白甲基化，表现为 H3K4-me2 水平的降低。除此之外，我们观察了肥胖小鼠胚胎中自噬和细胞凋亡的发生。有42个与自噬/凋亡相关的基因表达异常，LC3信号呈阳性，Clec16a、Rraga、Atg10水平降低。总之，我们的研究表明，肥胖通过诱导小鼠 DNA 损伤、异常组蛋白甲基化和自噬水平影响早期胚胎发育。

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Single‐cell transcriptome analysis reveals that maternal obesity affects DNA repair, histone methylation, and autophagy level in mouse embryos

Obesity causes many reproductive dysfunctions such as reduced conception, infertility, and early pregnancy loss, and this is largely due to the negative effects of obesity on oocyte and embryo quality. In the present study, we employed single‐cell RNA transcriptome sequencing to investigate the potential causes for the maternal obesity effects on mouse embryos. Our results showed that the 4‐cell and morula/blastocyst rates were all significantly decreased during embryo development in obese mice. Genome‐wide analysis indicated that obesity altered the expression of more than 1100 genes in 2‐cell embryos, including the genes which were related to the p53 signaling pathway and apoptosis. Further analysis showed that the expression of 47 genes related to DNA damage was changed, and a positive γH2A signal and the altered expression of Rad51 and Tex15 were observed in the obese embryos. Obesity also affected histone methylation, shown by the decrease of the H3K4‐me2 level. Besides this, we observed the occurrence of autophagy and apoptosis in the embryos of obese mice. There were 42 genes that were related to autophagy/apoptosis that showed aberrant expression, and the positive LC3 signal and the decrease of Clec16a, Rraga, and Atg10 level were also observed. In summary, our study suggested that obesity affected early embryonic development by inducing DNA damage, aberrant histone methylation, and autophagy levels in mice.

更新日期：2020-12-23

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