Rapamycin rescues the poor developmental capacity of aged porcine oocytes.
Rapamycin rescues the poor developmental capacity of aged porcine oocytes.
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DOI：
10.5713/ajas.2013.13816
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发表时间：
2014-05
期刊：
影响因子：
--
通讯作者：
Park SP
中科院分区：
文献类型：
--
作者：
Lee SE;Kim EY;Choi HY;Moon JJ;Park MJ;Lee JB;Jeong CJ;Park SP
未受精的卵母细胞在排卵后不可避免地老化，这限制了它们的可受精寿命和胚胎发育。雷帕霉素影响哺乳动物卵母细胞减数分裂成熟过程中雷帕霉素靶蛋白（mTOR）的表达和细胞骨架重组。本研究的目的是研究雷帕霉素处理对老化猪卵母细胞及其体外发育的影响。雷帕霉素处理老化卵母细胞24 h（68 h体外成熟[IVM]; 44 h+10 μM雷帕霉素/24 h，47.52±5.68）或对照卵母细胞（44 h IVM; 42.14±4.40）与未处理老化卵母细胞（68 h IVM，22.04±5.68）相比显著增加发育率和总细胞数（p<0.05）。与未处理的、24 h老化的IVM卵母细胞相比，雷帕霉素处理老化的IVM卵母细胞24 h还挽救了异常的纺锤体组织和染色体错位，阻断了磷酸化p44/42丝裂原活化蛋白激酶（MAPK）水平的降低，并增加了胞质成熟因子基因（MOS、BMP 15、GDF 9和CCNB 1）的mRNA表达（p<0.05）。此外，与对照或未处理的老化卵母细胞相比，雷帕霉素处理老化卵母细胞降低活性氧（ROS）活性和DNA片段化（p<0.05），并下调mTOR mRNA表达。相比之下，雷帕霉素处理老化卵母细胞增加线粒体定位，（p<0.05）并上调自噬mRNA的表达（BECN 1、ATG 7、MAP 1 LC 3B、ATG 12、GABARAP和GABARAPL 1），抗凋亡（BCL 2L 1和BIRC 5; p<0.05），和发育（NANOG和SOX 2; p<0.05）基因，但与对照相比，其不影响促凋亡基因（FAS和CASP 3）的mRNA表达。本研究表明，雷帕霉素处理可以挽救老化猪卵母细胞的发育能力差。
Unfertilized oocytes age inevitably after ovulation, which limits their fertilizable life span and embryonic development. Rapamycin affects mammalian target of rapamycin (mTOR) expression and cytoskeleton reorganization during oocyte meiotic maturation. The goal of this study was to examine the effects of rapamycin treatment on aged porcine oocytes and their in vitro development. Rapamycin treatment of aged oocytes for 24 h (68 h in vitro maturation [IVM]; 44 h+10 μM rapamycin/24 h, 47.52±5.68) or control oocytes (44 h IVM; 42.14±4.40) significantly increased the development rate and total cell number compared with untreated aged oocytes (68 h IVM, 22.04±5.68) (p<0.05). Rapamycin treatment of aged IVM oocytes for 24 h also rescued aberrant spindle organization and chromosomal misalignment, blocked the decrease in the level of phosphorylated-p44/42 mitogen-activated protein kinase (MAPK), and increased the mRNA expression of cytoplasmic maturation factor genes (MOS, BMP15, GDF9, and CCNB1) compared with untreated, 24 h-aged IVM oocytes (p<0.05). Furthermore, rapamycin treatment of aged oocytes decreased reactive oxygen species (ROS) activity and DNA fragmentation (p<0.05), and downregulated the mRNA expression of mTOR compared with control or untreated aged oocytes. By contrast, rapamycin treatment of aged oocytes increased mitochondrial localization (p<0.05) and upregulated the mRNA expression of autophagy (BECN1, ATG7, MAP1LC3B, ATG12, GABARAP, and GABARAPL1), anti-apoptosis (BCL2L1 and BIRC5; p<0.05), and development (NANOG and SOX2; p<0.05) genes, but it did not affect the mRNA expression of pro-apoptosis genes (FAS and CASP3) compared with the control. This study demonstrates that rapamycin treatment can rescue the poor developmental capacity of aged porcine oocytes.
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影响因子：
64.5
作者：
Mitsui, K;Tokuzawa, Y;Yamanaka, S
通讯作者：
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影响因子：
9.2
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