Chongqing Key Laboratory of Human Embryo Engineering, Center for Reproductive Medicine, Women and Children's Hospital of Chongqing Medical University, Chongqing, China.
Chongqing Clinical Research Center for Reproductive Medicine, Chongqing Health Center for Women and Children, Chongqing, China.
FASEB J. 2023 Jul;37(7):e23045. doi: 10.1096/fj.202300066RR.
Postovulatory aging can trigger deterioration of oocyte quality and subsequent embryonic development, and thus reduce the success rates of assisted reproductive technology (ART). The molecular mechanisms underlying postovulatory aging, and preventative strategies, remain to be explored. The near-infrared fluorophore IR-61, a novel heptamethine cyanine dye, has the potential for mitochondrial targeting and cell protection. In this study, we found that IR-61 accumulated in oocyte mitochondria and reduced the postovulatory aging-induced decline in mitochondrial function, including mitochondrial distribution, membrane potential, mtDNA number, ATP levels, and mitochondrial ultrastructure. In addition, IR-61 rescued postovulatory aging-caused oocyte fragmentation, defects in spindle structure, and embryonic developmental potential. RNA sequencing analysis indicated that the postovulatory aging-induced oxidative stress pathway might be inhibited by IR-61. We then confirmed that IR-61 decreased the levels of reactive oxygen species and MitoSOX, and increased GSH content in aged oocytes. Collectively, the results indicate that IR-61 may prevent postovulatory aging by rescuing oocyte quality, promoting successful rate in ART procedure.
排卵后老化会导致卵母细胞质量下降和随后的胚胎发育不良,从而降低辅助生殖技术 (ART) 的成功率。排卵后老化的分子机制和预防策略仍有待探索。近红外荧光染料 IR-61 是一种新型的七甲川花菁染料,具有靶向线粒体和细胞保护的潜力。在这项研究中,我们发现 IR-61 积累在卵母细胞的线粒体中,减少了排卵后老化引起的线粒体功能下降,包括线粒体分布、膜电位、mtDNA 数量、ATP 水平和线粒体超微结构。此外,IR-61 挽救了排卵后老化引起的卵母细胞碎片化、纺锤体结构缺陷和胚胎发育潜能下降。RNA 测序分析表明,IR-61 可能抑制了排卵后老化引起的氧化应激途径。然后我们证实,IR-61 降低了老化卵母细胞中活性氧和 MitoSOX 的水平,并增加了 GSH 的含量。总之,这些结果表明,IR-61 可能通过挽救卵母细胞质量来预防排卵后老化,提高 ART 程序的成功率。