Proteomic and metabolomic reveals abnormalities in metabolic processes, epigenetic modifications, oxidative stress, embryonic aneuploidy and implantation in mouse blastocysts derived from in vitro fertilization

Assisted reproductive technology (ART), especially in vitro fertilization (IVF), has become an important means of addressing infertility issues. Compared with natural conception (in vivo fertilization, IVO), IVF embryos are completely dependent on culture conditions, and the in vitro environment may interfere with early embryo gene expression, thereby affecting embryo development potential. However, various adverse outcomes in offspring have been reported to be associated with IVF, whereas limited research has been conducted on its effects during the early stages of embryonic development. This study aims to investigate the specific mechanisms by which ART affects blastocysts. Proteomics and metabolomics analyses were conducted to identify differentially expressed proteins and metabolites between IVO- and IVF-generated blastocysts, and enrichment analysis was performed on the differentially expressed proteins (DEPs). Proteomic analysis revealed 745 DEPs between the two groups, with 257 upregulated and 488 downregulated in IVF-derived blastocysts. Gene ontology (GO) enrichment analysis demonstrated that these DEPs were primarily associated in metabolic processes, epigenetic modifications, oxidative stress, embryonic aneuploidy, and implantation-related pathways. Conducted research of proteomic and metabolomic profiles of in vitro and in vivo retrieved embryos identified considerable amount of DEPs suggesting that altered protein expression maybe associated with the quality of blastocysts. These findings provide valuable insights for improving ART success rates and reducing health risks in IVF-conceived offspring, highlighting their significant clinical translational potential.