Inhibition of ferroptosis improves developmental competence of vitrified-warmed oocytes

Oocyte vitrification is widely used for female fertility preservation. However, current vitrification procedures can compromise oocyte quality, leading to increased oxidative stress and organelle dysfunction. Therefore, optimizing vitrification strategies to improve oocyte developmental competence is essential.

Mouse oocytes were randomly assigned to control (CON) and vitrification (VIT) groups. After storage in liquid nitrogen for over a month, vitrified oocytes were warmed and subjected to intracytoplasmic sperm injection (ICSI). Subsequent embryonic development was assessed in vitro. Transcriptomic and proteomic analyses were performed to identify differentially expressed genes and proteins, followed by validation using quantitative real-time PCR, immunofluorescence, and functional assays with the ferroptosis inhibitor ferrostatin-1 (Fer-1) and glutathione monoethyl ester (GSH-MEE).

Vitrification-warming impaired oocyte quality and reduced embryonic developmental competence in mouse oocytes. Vitrified-warmed oocytes exhibited mitochondrial dysfunction, increased oxidative stress, and enhanced lipid peroxidation. In addition, ferroptosis-related signaling was activated after vitrification-warming. Treatment with Fer-1 or GSH-MEE alleviated oxidative stress, improved mitochondrial function, and partially restored intracellular redox balance and iron homeostasis. Notably, both treatments significantly improved the developmental potential of vitrified-warmed oocytes.

Our findings suggest that vitrification-warming is associated with ferroptosis-related alterations in mouse oocytes. Inhibition of ferroptosis by Fer-1 or GSH-MEE partially improved oocyte quality and preimplantation embryonic development after cryopreservation.