image: Day 8 of human embryos: WNT pathway inhibition promotes epiblast development (arrows indicate proliferating epiblast)
Credit: ©Science China Press
Globally, approximately 186 million infertility patients rely on assisted reproductive technology (ART), yet the success rate per in vitro fertilization (IVF) cycle remains below 50%. This limitation is largely attributed to peri-implantation embryonic development - a critical phase marked by significant morphological changes and multi-lineage cell fate determination. However, due to technical limitations in conventional in vitro culture systems, research on peri-implantation embryonic development and implantation processes has remained relatively scarce.
Recently, a collaborative study led by Prof. Liu Wenqiang and Prof. Gao Shaorong from the School of Life Sciences and Technology, Tongji University, together with Prof. Li Kunming's team at the Tenth People's Hospital affiliated to Tongji University, was published online in Science Bulletin under the title "Persistent Wnt signaling affects IVF embryo implantation and offspring metabolism."
They reveal that persistent Wnt signaling during the peri-implantation stage may be a key obstacle to the implantation of IVF embryos in a mouse model. Wnt activation affects the deposition of H3K27ac and H3K27me3 on pluripotency genes and bivalent genes, respectively, leading to the abnormal naïve-primed transition and suppressing expression of Otx2 in the epiblast. Furthermore, treatment with the Wnt inhibitor IWP2 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. Moreover, Wnt inhibiting markedly improves human peri-implantation embryo development and facilitates the transition from a naïve pluripotency state. This study reveals a novel mechanism underlying the prevention of IVF embryo implantation failure and metabolic disorders in offspring.