Melatonin maintains mitochondrial membrane potential and decreases excessive intracellular Ca2+ levels in immature human oocytes
Melatonin maintains mitochondrial membrane potential and decreases excessive intracellular Ca2+ levels in immature human oocytes
复制标题
褪黑激素维持线粒体膜电位并降低未成熟人卵母细胞中过多的细胞内 Ca2 水平
DOI：
10.1016/j.lfs.2019.116810
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发表时间：
2019-10-15
期刊：
影响因子：
6.1
通讯作者：
Cao, Yun-Xia
中科院分区：
文献类型：
--
作者：
Liu, Ya-Jing;Ji, Dong-mei;Cao, Yun-Xia
目的：已有研究表明，褪黑素存在于松果体外的多个部位，且人卵泡液中的褪黑素含量高于血清，提示褪黑素可能在人卵母细胞成熟和胚胎发育过程中起重要作用。褪黑激素已被证明是一种有效的抗氧化剂，并可能有利于人类卵母细胞在体外成熟（IVM）。主要方法：采用免疫荧光染色、Western blotting、ELISA等方法检测体外培养的人卵巢卵丘细胞中褪黑素能成分的表达。主要研究结果：1、体外培养的人卵巢卵丘细胞能合成褪黑素，并表达褪黑素的前体5-羟色胺（serotonin，5-HT）和两种关键酶N-乙酰转移酶（N-acetyltransferase，NAT）和羟吲哚-O-甲基转移酶（hydroxydole-O-methyltransferase，HIOMT）。此外，结果表明，褪黑激素维持线粒体膜电位和减少过多的Ca 2+水平在未成熟的人卵母细胞在IVM。意义：总之，我们提供的证据表明，褪黑激素能成分在培养的人卵巢卵丘细胞中表达，褪黑激素可能会减少人卵母细胞的氧化应激，通过改善线粒体功能。鉴于未成熟人类卵母细胞在辅助生殖技术（ART）中的重要临床价值，我们的研究结果强调了在IVM期间使用褪黑激素改善线粒体功能并提高人类卵母细胞质量的潜在治疗策略。
Aims: Previous reports have demonstrated that melatonin exists in multiple extrapineal sites, and higher amounts of melatonin are present in human follicular fluid than in serum, which indicates that it might play key roles in human oocyte maturation and subsequent embryonic development. Melatonin has been shown to be a potent antioxidant and might be beneficial to human oocytes during in vitro maturation (IVM). However, the underlying mechanisms of melatonin action during IVM have not been thoroughly investigated.Main methods: Immunofluorescence staining, western blotting, and ELISA were applied to investigate whether melatoninergic components are expressed in the cultured human ovarian cumulus cells. TMRE staining and Fluo-4 AM staining were performed to detect the mitochondrial membrane potential and intracellular Ca2+ levels of immature human oocytes respectively.Key findings: First, cultured human ovary cumulus cells synthesized melatonin in vitro, and it expressed serotonin (the precursor of melatonin) and the two key enzymes, i.e. N-acetyltransferase (NAT) and hydroxyindole-O-methyltransferase (HIOMT). Additionally, the results suggest that melatonin maintains the mitochondrial membrane potential and decrease excessive Ca2+ levels in immature human oocytes during IVM.Significance: In conclusion, we provide evidence that the melatoninergic components were expressed in cultured human ovarian cumulus cells, and melatonin might reduce oxidative stress of human oocytes by ameliorating mitochondrial function. In view of the significant clinical value that immature human oocytes have in assisted reproductive technology (ART), our findings highlight a potential treatment strategy of using melatonin to improve mitochondrial function and to enhance the quality of human oocytes during IVM.