Methionine Adenosyltransferase 2β Participates in Mouse Oocyte Maturation by Regulating the MAPK Pathway

The methionine adenosyltransferase 2β gene (Mat2b) encodes for the regulatory subunit of methionine adenosyltransferase (MAT), which catalyzes the biosynthesis of S-adenosylmethionine. MAT2B interacts with G protein-coupled receptor kinase interacting ArfGAP1 to increase the activity of extracellular signal-regulated kinases (ERKs) for the regulation of cell growth, metabolism, and differentiation. ERK activity is also essential for oocyte meiosis in mice. However, the regulatory role of MAT2B in mouse oocyte meiosis remains unclear. Accordingly, this study investigated the effect of MAT2B on mouse oocyte maturation. Immunostaining showed that MAT2B localized predominantly in the nucleus of fully grown germinal vesicle (GV) oocytes. After germinal vesicle breakdown (GVBD), MAT2B homogeneously localized in the cytoplasm. A low oocyte maturation rate was observed in Mat2b siRNA-treated oocytes. Furthermore, Mat2b knockdown repressed the phosphorylation of ERK1/2 and consequently blocked MAPK. Denuded oocytes treated with 20 μM U0126 mainly blocked MAPK phosphorylation and affected oocyte maturation. The oocytes arrested at GVBD and metaphase I (MI) by Mat2b silencing or U0126 treatment had several types of abnormal microtubule assembly. Furthermore, Mat2b knockdown or U0126 treatment resulted in the aberrant expression of six maternal transcripts, namely, Fgf8, Cdc2, Gdf9, Padi6, Polr2d, and Tecb2. To the best of our knowledge, this study is the first to demonstrate that Mat2bs play an important role in mouse oocyte maturation though MAPK signaling.