Role of methionine adenosyltransferase 2A in bovine preimplantation development and its associated genomic regions

Shuntaro Ikeda,Hisataka Iwata,Miki Sugimoto,Ryouka Kawahara-Miki,Shinichi Kume

doi:10.1038/s41598-017-04003-1

Shuntaro Ikeda, Hisataka Iwata + Show 3 more

Open Access

https://doi.org/10.1038/s41598-017-04003-1

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Abstract

Methionine adenosyltransferase (MAT) is involved in folate-mediated one-carbon metabolism, which is essential for preimplantation embryos in terms of both short-term periconceptional development and long-term phenotypic programming beyond the periconceptional period. Here, our immunofluorescence analysis of bovine oocytes and preimplantation embryos revealed the consistent expression of MAT2A (the catalytic subunit of the ubiquitously expressed-type of MAT isozyme) during this period. Addition of the MAT2A inhibitor FIDAS to the culture media of bovine preimplantation embryos reduced their blastocyst development, revealing the particular importance of MAT2A in successful blastocyst development. Exploration of MAT2A-associated genomic regions in bovine blastocysts using chromatin immunoprecipitation and sequencing (ChIP-seq) identified candidate MAT2A-associated genes implicated not only in short-term periconceptional embryo development, but also in long-term phenotypic programming during this period in terms of growth, metabolism, and immune functions. These results suggest the critical involvement of MAT2A in the periconceptional period in life-long programming of health and disease as well as successful preimplantation development.

Highlights

The periconceptional period of mammalian embryo development is a critical window during which diverse environmental conditions, including available nutrients, have short-term effects on aspects such as cellular proliferation, and long-term effects on metabolic and developmental processes throughout gestation and even during postnatal life[1]
Three Methionine adenosyltransferase (MAT) genes (MAT1A, MAT2A, and MAT2B) encode three MAT isozymes; the MATI and MATIII isozymes are a tetramer and dimer, respectively, of an identical catalytic subunit encoded by the MAT1A gene, whereas the MATII isozyme is a hetero-oligomer consisting of catalytic subunit(s) encoded by MAT2A and regulatory subunit(s) encoded by MAT2B3
We found that bovine preimplantation embryos expressed MAT1A transcripts, which disappeared from the 8-cell stage onwards, with MAT1A protein decreasing from the morula stage, whereas MAT2A and MAT2B transcripts were expressed throughout the preimplantation development[8]

Summary

Introduction

The periconceptional period of mammalian embryo development is a critical window during which diverse environmental conditions, including available nutrients, have short-term effects on aspects such as cellular proliferation, and long-term effects on metabolic and developmental processes throughout gestation and even during postnatal life[1]. Preimplantation development is a period of dynamic epigenetic rearrangement involving substantial changes in DNA methylation and histone modifications, which may affect the regulation of specific and heritable patterns of gene expression[1, 2]. The involvement of OCM in epigenetic modification of gene expression is of interest, in terms of successful embryonic development, and in relation to its possible association with nutrition-dependent phenotypic programming during the periconceptional period[14,15,16]. In the context of long-term phenotypic programming by OCM modulation during the periconceptional period[14,15,16], possible interactions between MAT2A and the epigenetic status of specific genes are of particular interest.

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