Laboratory of Animal Physiology and Functional Anatomy, Graduate School of Agriculture, Kyoto University, Kyoto, 606-8502, Japan.
NODAI Genome Research Center, Tokyo University of Agriculture, Tokyo, 156-8502, Japan.
Sci Rep. 2017 Jun 19;7(1):3800. doi: 10.1038/s41598-017-04003-1.
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.
蛋氨酸腺苷转移酶（MAT）参与叶酸介导的一碳代谢，对于植入前胚胎的短期围孕期发育和围孕期后长期表型编程都至关重要。在这里，我们通过免疫荧光分析牛卵母细胞和植入前胚胎，发现 MAT2A（普遍表达型 MAT 同工酶的催化亚基）在这段时间内持续表达。在牛植入前胚胎的培养基中添加 MAT2A 抑制剂 FIDAS 会降低其囊胚发育率，这表明 MAT2A 对囊胚发育的成功至关重要。使用染色质免疫沉淀和测序（ChIP-seq）技术探索牛囊胚中与 MAT2A 相关的基因组区域，鉴定出候选的与 MAT2A 相关的基因，这些基因不仅与短期围孕期胚胎发育有关，而且与围孕期后的生长、代谢和免疫功能等长期表型编程有关。这些结果表明，MAT2A 在围孕期对健康和疾病的终身编程以及成功的植入前发育都具有关键作用。
