Iron Overload-Induced Ferroptosis Impairs Porcine Oocyte Maturation and Subsequent Embryonic Developmental Competence in vitro.
Iron Overload-Induced Ferroptosis Impairs Porcine Oocyte Maturation and Subsequent Embryonic Developmental Competence in vitro.
复制标题
铁过载诱导的铁死亡会损害猪卵母细胞的成熟和随后的体外胚胎发育能力
DOI：
10.3389/fcell.2021.673291
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发表时间：
2021
影响因子：
5.5
通讯作者：
Liang S
中科院分区：
文献类型：
--
作者：
Hu W;Zhang Y;Wang D;Yang T;Qi J;Zhang Y;Jiang H;Zhang J;Sun B;Liang S
越来越多的证据表明，铁凋亡是一种铁依赖性的调节性细胞死亡形式。这种类型的铁依赖性程序性细胞死亡不同于传统形式的调节性细胞死亡，如凋亡和自噬。然而，铁凋亡在猪卵母细胞成熟中的作用及其相关机制尚不清楚。本研究探讨了特异性铁凋亡诱导剂柠檬酸铁铵（FAC）对猪卵母细胞减数分裂成熟、质量及胚胎发育能力的影响。FAC处理引起猪卵母细胞内亚铁离子的明显积累。在体外成熟（IVM）期结束时，FAC处理组的极体（PB）排出率显著降低，异常卵母细胞的百分比增加，表明铁过载诱导的铁凋亡可能抑制猪卵母细胞成熟过程中的减数分裂过程。结果表明，FAC处理后，猪孤雌激活（PA）胚胎的2-细胞率、4-细胞率和囊胚形成率均显著降低，表明铁过量诱导的铁凋亡降低了猪卵母细胞的质量。进一步的分析表明，FAC处理不仅增强细胞内活性氧（ROS）的产生，降低细胞内游离巯基水平，诱导线粒体功能障碍，而且还引发猪卵母细胞的自噬。总之，这些研究结果表明，铁过载诱导的铁凋亡损害猪卵母细胞减数分裂，降低猪卵母细胞的质量，可能是通过增加氧化应激，诱导线粒体功能障碍和触发自噬。
Accumulating evidence indicates that ferroptosis is an iron-dependent form of regulated cell death. This type of iron-dependent programmed cell death is different from traditional forms of regulated cell death, such as apoptosis and autophagy. However, the role of ferroptosis in porcine oocyte maturation and the associated mechanism remain unclear. In the present research, we investigated the effects of ferric ammonium citrate (FAC), a specific ferroptosis inducer, on porcine oocyte meiotic maturation and quality and subsequent embryonic developmental competence. FAC treatment caused obvious accumulation of intracellular ferrous ions in porcine oocytes. At the end of the in vitro maturation (IVM) period, there was a significant decrease in the polar body (PB) extrusion rate and an increase in the percentage of abnormal oocytes in the FAC treatment groups, indicating that iron overload-induced ferroptosis may suppress the meiotic process during porcine oocyte maturation. We also found that after FAC treatment, the subsequent two-cell rate, four-cell rate and blastocyst formation rate were significantly decreased in porcine parthenogenetic activation (PA) embryos, indicating that iron overload-induced ferroptosis decreased porcine oocyte quality. Further analysis revealed that FAC treatment not only enhanced intracellular reactive oxygen species (ROS) generation, decreased intracellular free thiol levels and induced mitochondrial dysfunction but also triggered autophagy in porcine oocytes. Taken together, these findings suggest that iron overload-induced ferroptosis impairs porcine oocyte meiosis and decreases porcine oocyte quality, possibly by increasing oxidative stress, inducing mitochondrial dysfunction and triggering autophagy.
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影响因子：
64.5
作者：
Dixon SJ;Lemberg KM;Lamprecht MR;Skouta R;Zaitsev EM;Gleason CE;Patel DN;Bauer AJ;Cantley AM;Yang WS;Morrison B 3rd;Stockwell BR
通讯作者：
Stockwell BR
影响因子：
5
作者：
Khamseekaew, Juthamas;Kumfu, Sirinart;Chattipakorn, Nipon
通讯作者：
Chattipakorn, Nipon
影响因子：
6.1
作者：
Ferrer-Vaquer, A.;Barragan, M.;Vassena, R.
通讯作者：
Vassena, R.
DOI：
10.1262/jrd.2013-115
发表时间：
2014-04-24
期刊：
The Journal of reproduction and development
影响因子：
--
作者：
Koyama K;Kang SS;Huang W;Yanagawa Y;Takahashi Y;Nagano M
通讯作者：
Nagano M
DOI：
10.1124/jpet.118.252759
发表时间：
2019-04-01
影响因子：
3.5
作者：
Cotticelli, M. Grazia;Xia, Shujuan;Wilson, Robert B.
通讯作者：
Wilson, Robert B.