Ectopic histone modification in extra-embryonic tissues influence implantation and placenta development of IVF embryos (ChIP-Seq)

Assisted reproductive technology (ART), especially in vitro fertilization (IVF) and embryo transfer have been widely applied in the treatment of human infertility. However, the accumulating evidences indicate that IVF is associated with low pregnancy rate, placental defect and the metabolic diseases in offspring. Here, we identify ectopic histone H3K4me3 in extraembryonic ectoderm (ExE) as an important reason for embryo implantation failure and extra-embryonic development abnormalities of IVF embryos. IVF manipulation notably disrupt extra-embryonic tissue-specific gene expression, 334 epiblast (Epi)-specific genes and 24 Epi-specific transcription factors were abnormally expressed in ExE of IVF embryos at embryonic day 7.5 (E7.5). Combined histone modification analysis reveal that ectopic H3K4me3 modification at the Epi-active promoter resulted in increased expression of these genes in ExE of IVF embryos at E7.5. By konckdown the expression of H3K4me3 recruited regulator Kmt2e, which highly expressed in IVF embryos, can improve the development of IVF embryo and reduce the abnormal gene expression in ExE. Therefore, our research identifies the abnormal H3K4me3 modification occupied in extra-embryonic tissue may be an important reason for implantation failure and abnormal placental development of IVF embryo. To precisely dissect the histone changes of IVF embryos, we generated a H3K4me3 and H3K27me3 landscapes of morula, E3.5 blastocyst (TE, ICM), E7.5 embryos (ExE, Epi) respectively from IVF and NM embryos by ULI-NChIP