Integrated Glycosylation Patterns of Glycoproteins and DNA Methylation Landscapes in Mammal Oogenesis and Preimplantation Embryo Development

Abstract

Background: Post-translational modification is a crucial event during mammalian embryonic development. Glycosylation is one of the most fundamental post-translational modifications. However, the glycosylation patterns of glycoproteins have not been analyzed in mammal preimplantation embryos, because of technical difficulties and scarcity of required materials. Methods: This study investigated the glycosylation patterns of glycoproteins and DNA methylation landscapes in mammal oogenesis and preimplantation embryo development by high-throughput lectin microarray of low-input cells, electrochemical techniques, and genome-wide DNA methylation analysis. Finding: We showed that there were dramatic changes in protein glycosylation levels that occur during mammal oogenesis and preimplantation embryo development. Further analysis identified several stage-specific lectins, such as MNA-M, ABA, and MAL I. Subsequent results showed that the variation tendencies of glycosylation patterns of glycoproteins were opposite to the TET levels during oogenesis and preimplantation embryo development. Moreover, analysis of correlation between the changes in glyco-gene expression and female germline stem cell glycosylation profiles indicated that glycosylation was related to DNA methylation. Subsequent integration analysis showed that the tendency variations of glycosylation patterns of glycoproteins were similar to that of DNA methylation, and opposite to the TET protein levels during female germ cell and preimplantation embryo development. Interpretation: Our findings provide insight into the complex molecular mechanisms that regulate human embryo development, and a foundation that can be used to help further elucidate early embryonic development and inform reproductive medicine. Funding Statement: This work was supported by National Basic Research Program of China (2018YFC1003501, 2017YFA0504201), National Nature Science Foundation of China (81720108017), the National Major Scientific Instruments and Equipment Development Project, National Nature Science Foundation of China (61827814). Declaration of Interests: The authors declare no conflict of interest. Ethics Approval Statement: Animal experimentation was approved by the Institutional Animal Care and Use Committee of Shanghai and performed in accordance with the National Research Council Guide for Care and Use of Laboratory Animals.