Laboratory of Biotechnology of Reproduction, Institute for Animal Science and Technology (ICTA), Universitat Politècnica de Valencia, 46022 Valencia, Spain.
Casaccia Research Centre, Italian National Agency for New Technologies, Energy and Sustainable Development (ENEA), 00123 Rome, Italy.
Int J Mol Sci. 2021 Sep 8;22(18):9716. doi: 10.3390/ijms22189716.
Embryo manipulation is a requisite step in assisted reproductive technology (ART). Therefore, it is of great necessity to appraise the safety of ART and investigate the long-term effect, including lipid metabolism, on ART-conceived offspring. Augmenting our ART rabbit model to investigate lipid metabolic outcomes in offspring longitudinally, we detected variations in hepatic DNA methylation ART offspring in the F3 generation for embryonic exposure (multiple ovulation, vitrification and embryo transfer). Through adult liver metabolomics and proteomics, we identified changes mainly related to lipid metabolism (e.g., polyunsaturated fatty acids, steroids, steroid hormone). We also found that DNA methylation analysis was linked to changes in lipid metabolism and apoptosis genes. Nevertheless, these differences did not apparently alter the general health status. Thus, our findings suggest that ART is likely to be a player in embryo epigenetic events related to hepatic homeostasis alteration in adulthood.
胚胎操作是辅助生殖技术（ART）的必要步骤。因此，评估 ART 的安全性并研究其对 ART 受孕后代的长期影响（包括脂质代谢）非常必要。为了通过我们的 ART 兔模型从纵向角度研究后代的脂质代谢结果，我们检测了胚胎暴露（多排卵、玻璃化和胚胎移植）的 F3 代后代的肝 DNA 甲基化 ART 后代中的变化。通过成年肝脏代谢组学和蛋白质组学，我们确定了主要与脂质代谢相关的变化（例如，多不饱和脂肪酸、类固醇、甾体激素）。我们还发现，DNA 甲基化分析与脂质代谢和细胞凋亡基因的变化有关。然而，这些差异并没有明显改变一般健康状况。因此，我们的研究结果表明，ART 可能是与成年期肝内稳态改变相关的胚胎表观遗传事件的参与者。
