Near‐infrared fluorophore IR‐61 delays postovulatory aging of mouse oocytes through suppressing oxidative stress mediated by mitochondrial protection

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. IR‐61 targets oocyte mitochondria and improves postovulatory aged oocyte quality by reducing oxidative stress and thus protecting mitochondria. IR‐61 prevents postovulatory oocyte aging and may improve the success rate of human ART.