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.

译文

蛋氨酸腺苷转移酶 (MAT) 参与叶酸介导的单碳代谢,这对于植入前胚胎的短期围术期发展和围术期以后的长期表型编程都是必不可少的。在这里,我们对牛卵母细胞和植入前胚胎的免疫荧光分析揭示了在此期间MAT2A (MAT同工酶普遍表达类型的催化亚基) 的一致表达。在牛植入前胚胎的培养基中添加MAT2A抑制剂FIDAS会降低其胚泡发育,从而揭示了MAT2A在成功胚泡发育中的特殊重要性。使用染色质免疫沉淀和测序 (ChIP-seq) 探索牛囊胚中的MAT2A-associated基因组区域,确定了候选MAT2A-associated基因,不仅涉及短期内胚胎发育,而且还涉及在此期间生长,代谢和免疫功能方面的长期表型编程。这些结果表明,MAT2A在围手术期的关键参与了健康和疾病的终生规划以及成功的植入前发展。

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