Persistent Wnt signaling affects IVF embryo implantation and offspring metabolism (PRJCA026489)

Persistent Wnt signaling during the peri-implantation stage may be a key obstacle to the implantation failure of in vitro fertilization (IVF) embryos. WNT activation affects the deposition of H3K27ac and H3K27me3 on pluripotency genes and bivalent genes, respectively, leading to the abnormal naive-primed transition and suppressing expression of Otx2 in epiblast. Furthermore, treatment with the Wnt inhibitor IWP2 that promotes the redistribution of histone modifications and gene expression of epiblast. Importantly, Wnt inhibiting significantly improves implantation and intrauterine development of IVF embryos and subsequently ameliorates offspring metabolic abnormalities. Our study reveals a novel mechanism underlying the prevention of IVF embryo implantation failure and metabolic disorders in offspring.