Abstract：
Ferroptosis suppressor protein 1 (FSP1) is a glutathione-independent ferroptosis inhibitory factor. FSP1 has been found to play a crucial role in the regulation of mitochondrial function and ferroptosis. However, its function in porcine early embryonic development remains unknown. In the present research, we found that FSP1 was expressed at different stages during porcine early embryo development. Compared with the control condition, inhibition of FSP1 reduced the cleavage rate at 24 h and 48 h and the blastocyst rate at 144 h. In addition, inhibiting FSP1 reduced the blastocyst diameter, total cell number, and proliferation capacity. Further analysis showed that inhibition of FSP1 significantly increased the levels of ferrous ions (Fe2+) and MDA but not GPX4. We also found that inhibition of FSP1 significantly decreased mitochondrial membrane potential and ATP levels, which in turn caused excessive accumulation of ROS and decreased the levels of GSH and the activity of the intracellular antioxidant enzymes SOD and CAT in embryos. In conclusion, FSP1, an important regulator, participates in regulating the development and quality of porcine early embryos. Inhibition of FSP1 impairs blastocyst formation, induces glutathione-independent ferroptosis, and further leads to oxidative stress due to mitochondrial dysfunction, ultimately affecting the developmental competence and impairing the quality of porcine early embryos.
摘要：
铁凋亡抑制蛋白1(FSP1)是一种不依赖谷胱甘肽的铁凋亡抑制因子。已发现FSP1在线粒体功能和铁凋亡的调节中起关键作用。然而,其在猪早期胚胎发育中的作用尚不清楚。在目前的研究中,我们发现FSP1在猪早期胚胎发育的不同阶段都有表达。与控制条件相比，FSP1的抑制降低了24小时和48小时的卵裂率和144小时的胚泡率。抑制FSP1降低了胚泡直径，细胞总数,和扩散能力。进一步分析显示,FSP1的抑制显著增加亚铁离子(Fe2+)和MDA的水平,但不增加GPX4的水平。我们还发现抑制FSP1显著降低线粒体膜电位和ATP水平,这反过来又导致了ROS的过度积累，并降低了GSH的水平以及胚胎中细胞内抗氧化酶SOD和CAT的活性。总之,FSP1，一个重要的调节器，参与调节猪早期胚胎的发育和质量。抑制FSP1损害胚泡形成，诱导谷胱甘肽非依赖性铁死亡，并进一步导致线粒体功能障碍引起的氧化应激，最终影响猪早期胚胎的发育能力和质量。
