Integration of transcriptome and chromatin accessibility in embryos developed in vivo or in vitro
Résumé
Embryonic preimplantation development is a highly dynamic process, involving the embryonic genome activation and the differentiation of the first cells. This process, which is tightly regulated epigenetically, ensures the development of the fetus and the extraembryonic tissues. With the increasing use of assisted reproductive technologies, safety concerns, especially during in vitro culture, have become a major public health issue. To identify the impact of in vitro culture on the first embryonic lineages, we analysed gene expression and chromatin accessibility in rabbit embryos developed either in vivo or in vitro. The rabbit was chosen as a model because its characteristics are close to those of the human embryo (i.e. timing of EGA, metabolism). Embryos developed in vivo were harvested at 86 hours post-coitum (hpc) (early blastocyst) and at 96 hpc (mid blastocyst). Embryos developed in vitro were produced by culture from the zygote. The inner cell mass (ICM) and the trophectoderm (TE) were separated by immunosurgery. Genome wide transcriptome and chromatin accessibility were profiled by RNA-seq and ATAC-seq, respectively. Genes involved in metabolic pathways such as oxidative phosphorylation, Krebs cycle, mTORC1 and fatty acid metabolism were less expressed in ICM and TE from in vitro than in vivo developed embryos. Genes involved in gene expression regulation and chromatin organization were more highly expressed in ICM and TE from in vitro than in vivo developed embryos. Vitro-TE exhibited more similarities with vivo-TE from early embryos and inversely, vitro-ICM exhibited more similarities with vivo-ICM from mid embryos. We observed major differences in transcriptome and chromatin accessibility in both ICM and TE between embryos developed in vivo and in vitro. These dissimilarities may be involved in long-term effects.