Fertility Preservation Lab, Reproductive Medicine Center, Guangdong Second Provincial General Hospital, Guangzhou, China.
College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, China.
J Cell Physiol. 2021 Jul;236(7):4944-4953. doi: 10.1002/jcp.30201. Epub 2020 Dec 23.
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.
肥胖会导致许多生殖功能障碍，如受孕率降低、不孕以及早期妊娠丢失，这在很大程度上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 转录组测序来研究肥胖对母鼠胚胎影响的潜在原因。我们的结果表明，肥胖小鼠胚胎发育过程中的 4 细胞和桑椹胚/囊胚率均显著降低。全基因组分析表明，肥胖改变了 2 细胞胚胎中超过 1100 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改变，并且在肥胖胚胎中观察到阳性 γH2A 信号和 Rad51 和 Tex15 的表达改变。肥胖还影响组蛋白甲基化，表现为 H3K4-me2 水平降低。除此之外，我们还观察到肥胖小鼠胚胎中自噬和细胞凋亡的发生。有 42 个与自噬/细胞凋亡相关的基因表达异常，并且还观察到阳性 LC3 信号和 Clec16a、Rraga 和 Atg10 水平降低。总之，我们的研究表明，肥胖通过诱导 DNA 损伤、异常的组蛋白甲基化和自噬水平影响小鼠早期胚胎发育。
