Melatonin significantly improves the developmental competence of bovine somatic cell nuclear transfer embryos
Melatonin significantly improves the developmental competence of bovine somatic cell nuclear transfer embryos
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褪黑素显着提高牛体细胞核移植胚胎的发育能力
DOI：
10.1111/jpi.12275
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发表时间：
2015-11-01
影响因子：
10.3
通讯作者：
Zhang, Yong
中科院分区：
文献类型：
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作者：
Su, Jianmin;Wang, Yongsheng;Zhang, Yong
体细胞核移植(SCNT)是一项很有前途的技术，但其效率较低，阻碍了其应用。因此，大多数SCNT胚胎无法发育到足月。在这项研究中，抗氧化剂褪黑素减少了牛SCNT胚胎的细胞凋亡和活性氧(ROS)。在促进牛SCNT胚胎体外和体内发育的同时，还增加了细胞数、内细胞质量(ICM)细胞数和ICM/总细胞的比例。基因表达分析表明，褪黑素抑制了SCNT囊胚中促凋亡基因P53和Bax的表达，刺激了抗氧化基因SOD1和Gpx4、抗凋亡基因BCL2L1和多能性相关基因SOX2的表达。我们还分析了牛体外受精、褪黑素处理和未处理的SCNT胚胎的表观遗传修饰。褪黑激素处理的四细胞期SCNT胚胎的全球H3K9ac水平高于未处理的SCNT胚胎。我们的结论是，外源褪黑素影响与细胞凋亡、抗氧化功能和发育相关的基因的表达。此外，褪黑素还能减少牛SCNT胚胎的细胞凋亡和ROS，提高囊胚质量，从而最终提高牛的克隆效率。
Somatic cell nuclear transfer (SCNT) is a promising technology, but its application is hampered by its low efficiency. Hence, the majority of SCNT embryos fail to develop to term. In this study, the antioxidant melatonin reduced apoptosis and reactive oxygen species (ROS) in bovine SCNT embryos. It also increased cell number, inner cell mass (ICM) cell numbers, and the ratio of ICM to total cells while improving the development of bovine SCNT embryos in vitro and in vivo. Gene expression analysis showed that melatonin suppressed the expression of the pro‐apoptotic genes p53 and Bax and stimulated the expression of the antioxidant genes SOD1 and Gpx4, the anti‐apoptotic gene BCL2L1, and the pluripotency‐related gene SOX2 in SCNT blastocysts. We also analyzed the epigenetic modifications in bovine in vitro fertilization, melatonin‐treated, and untreated SCNT embryos. The global H3K9ac levels of melatonin‐treated SCNT embryos at the four‐cell stage were higher than those of the untreated SCNT embryos. We conclude that exogenous melatonin affects the expression of genes related to apoptosis, antioxidant function, and development. Moreover, melatonin reduced apoptosis and ROS in bovine SCNT embryos and enhanced blastocyst quality, thereby ultimately improving bovine cloning efficiency.