Reactive oxygen species (ROS) involve in oocyte postovulatory aging, yet the mechanism of ROS accumulation is not fully understood. We explored iron metabolic status and its relationship with ROS in mouse oocytes during postovulatory aging in vivo. We found that heme oxygenase 1 (HO-1) expression was increased in oviduct and iron metabolism was disordered in oocytes with time post-ovulation. The aging oocytes were manifested with high iron content and disturbed expressions of iron metabolic proteins, including ferritin heavy chain (FHC), mitochondrial ferritin (FtMT), divalent metal transporter 1 (DMT1), ferroportin1 (FPN1), iron regulatory protein 2 (IRP2) and transferrin receptor 1 (TFR1), along with increased cytosolic free Fe2+, lipid peroxidation, DNA damage, mitochondrial and lysosomal abnormality, and defects in spindle and chromosome alignment. These in vivo aging cells contained stable glutathione peroxidase 4 (GPX4) and 4-hydroxynonenal (4-HNE), unexpectedly, but had more iron and degenerative changes than their in vitro counterparts. The intraperitoneal deferoxamine (DFO) could alleviate all these changes and improve the fertilization competence and preimplantation development. Similarly, the HO-1 inhibitor Zinc Protoporphyrin (ZnPP) also could do this. Together, the iron homeostasis disturbance participates in ROS accumulation and degenerative changes in postovulatory aging oocytes, which can be alleviated by iron chelating.
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