摘要
Assisted reproductive technology(ART)is associated with increased implantation failure and subsequent metabolic abnormalities in offspring,but the underlying mechanisms remain largely elusive.Here,we reveal that persistent Wnt signaling during the peri-implantation stage may be a key obstacle to the implantation of in vitro fertilization(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.Our study reveals a novel mechanism underlying the prevention of IVF embryo implantation failure and metabolic disorders in offspring.
基金
supported by the National Key R&DProject of China(2022YFC2702200 and 2021YFA1102900)
the National Natural Science Foundation of China(32488101,32330030,82301921,32270909,82201881,92168205,31871448,31820103009,82022027,and 32300684)
supported by the key project of the Science and Technology of Shanghai Municipality(19JC1415300 and 21JC1405500)
the Natural Science Foundation of Shanghai(21ZR1450700)
the ChinaPostdoctoral Science Foundation(2023M732660)
the PostdoctoralFellowship Program of CPSF(GZB20230523)
the Shanghai PilotProgram for Basic Research,the Shanghai Post-doctoral ExcellenceProgram(2022521,2022551,and 2023616)
the China postdoctoral science foundation(2023M732660)
the Postdoctoral Fellowship Program of CPSF(GZB20230523)
the Fundamental Research Funds for the Central Universities(22120240435)
the ShenzhenMedical Research Fund(B2402013)
Peak Disciplines(TypeIV)of Institutions of Higher Learning in Shanghai.
