Glycine regulates lipid peroxidation promoting porcine oocyte maturation and early embryonic development
Glycine regulates lipid peroxidation promoting porcine oocyte maturation and early embryonic development
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甘氨酸调节脂质过氧化促进猪卵母细胞成熟和早期胚胎发育
DOI：
10.1093/jas/skac425
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发表时间：
2022
影响因子：
3.3
通讯作者：
Suo Li
中科院分区：
文献类型：
--
作者：
Lepeng Gao;Chang Zhang;Yingying Zheng;Deyi Wu;Xinyuan Chen;Hainan Lan;Xin Zheng;Hao Wu;Suo Li
体外培养的卵母细胞与体内卵泡微环境分离，比体内卵母细胞更容易受到外界环境变化的影响。这种脆弱性破坏了细胞内环境的稳态，影响卵母细胞减数分裂的完成以及随后的体外胚胎发育能力。甘氨酸是谷胱甘肽（GSH）的主要成分之一，在体外保护猪卵母细胞中发挥着重要作用。然而，甘氨酸的保护机制有待进一步阐明。我们的结果表明，补充甘氨酸促进卵丘细胞扩张和卵母细胞成熟。卵母细胞发育能力检测表明，甘氨酸显着提高体外受精（IVF）过程中的卵裂率和囊胚率。 SMART-seq揭示这种效应与甘氨酸介导的细胞膜结构和功能调节有关。外源添加甘氨酸显着增加抗氧化 GSH 水平和抗氧化相关基因（谷胱甘肽过氧化物酶 4 [GPX4]、过氧化氢酶 [CAT]、超氧化物歧化酶 1 [SOD1]、超氧化物歧化酶 2 [SOD2] 和线粒体溶质载体家族 25，成员 39 [SLC25A39]）的表达，降低 通过增强线粒体、过氧化物酶体和脂滴（LD）的功能以及脂质代谢相关因子（过氧化物酶体增殖物激活受体辅激活物1α[PGC-1α]、过氧化物酶体）的水平，消除活性氧（ROS）引起的脂质过氧化，降低丙二醛（MDA）水平 增殖剂激活受体 γ [PPARγ]、甾醇调节元件结合因子 1 [SREBF1]、自分泌运动因子受体 [AMFR] 和 ATP）。这些作用进一步减少铁死亡并维持细胞膜的正常结构和功能。我们的结果表明，甘氨酸通过调节 ROS 诱导的脂质代谢，从而防止生物膜损伤，在卵母细胞成熟和后期发育中发挥重要作用。
In vitro-cultured oocytes are separated from the follicular micro-environment in vivo and are more vulnerable than in vivo oocytes to changes in the external environment. This vulnerability disrupts the homeostasis of the intracellular environment, affecting oocyte meiotic completion, and subsequent embryonic developmental competence in vitro. Glycine, one of the main components of glutathione (GSH), plays an important role in the protection of porcine oocytes in vitro. However, the protective mechanism of glycine needs to be further clarified. Our results showed that glycine supplementation promoted cumulus cell expansion and oocyte maturation. Detection of oocyte development ability showed that glycine significantly increased the cleavage rate and blastocyst rate during in vitro fertilization (IVF). SMART-seq revealed that this effect was related to glycine-mediated regulation of cell membrane structure and function. Exogenous addition of glycine significantly increased the levels of the anti-oxidant GSH and the expression of anti-oxidant-related genes (glutathione peroxidase 4 [GPX4], catalase [CAT], superoxide dismutase 1 [SOD1], superoxide dismutase 2 [SOD2], and mitochondrial solute carrier family 25, member 39 [SLC25A39]), decreased the lipid peroxidation caused by reactive oxygen species (ROS) and reduced the level of malondialdehyde (MDA) by enhancing the functions of mitochondria, peroxisomes and lipid droplets (LDs) and the levels of lipid metabolism-related factors (peroxisome proliferator activated receptor coactivator 1 alpha [PGC-1α], peroxisome proliferator-activated receptor γ [PPARγ], sterol regulatory element binding factor 1 [SREBF1], autocrine motility factor receptor [AMFR], and ATP). These effects further reduced ferroptosis and maintained the normal structure and function of the cell membrane. Our results suggest that glycine plays an important role in oocyte maturation and later development by regulating ROS-induced lipid metabolism, thereby protecting against biomembrane damage.