A genome-wide association study to identify PPARγinvolved metabolic abnormalities by oxidative damage in IVF offspring

Based on our previous animal model of abnormal metabolism, we combined bioinformatics methods to explore the mechanism of early embryo oxidative stress increasing metabolic risk in offspring. Methods: To screen the differentially expressed genes (DEGs) between IVF and naturally conceived offspring by bioinformatics methods, and to identify the co-gene characteristics and biological function mechanisms of DEGs and glucose and lipid metabolism related. Then, we constructed oxidative stress models in vitro and in vivo and performed functional analysis of early embryo differential genes caused by oxidative stress to explore the molecular mechanism of abnormal metabolism risk in IVF offspring. Results: In IVF offspring, we found 15 differentially expressed genes associated with disorders of glucose and lipid metabolism, and their biological functions are primarily associated with lipid metabolism. Zygote oxidative stress is a key factor affecting offspring health, and in different oxidative stress models, the level of ROS was significantly increased. More importantly, the PPAR pathway was altered in both IVF offspring and the early embryo oxidative stress model. In addition, we found decreased expression and nuclear localization of PPARγ in oxidative stress on IVF-derived embryos. Conclusion: The results suggest that PPARγ is involved in the development of embryos under oxidative stress. Oxidative stress can lead to genome-wide reprogramming of embryos and affect The long-term health of offspring through PPARγ.