Ann Nakai, Yuki Fukushima, Ayaka Yamamoto, Yuki Amatsu, Xiaoyan Chen, Mitsuhiro Nishigori, Yukino Yoshioka, Mari Kaneko, Takumi Koshiba, Toshio Watanabe
FEBS letters 2024 JulReactive oxygen species (ROS) are associated with oocyte maturation inhibition, and N-acetyl-l-cysteine (NAC) partially reduces their harmful effects. Mitochondrial E3 ubiquitin ligase 1 (Mul1) localizes to the mitochondrial outer membrane. We found that female Mul1-deficient mice are infertile, and their oocytes contain high ROS concentrations. After fertilization, Mul1-deficient embryos showed a DNA damage response (DDR) and abnormal preimplantation embryogenesis, which was rescued by NAC addition and ROS depletion. These observations clearly demonstrate that loss of Mul1 in oocytes increases ROS concentrations and triggers DDR, resulting in abnormal preimplantation embryogenesis. We conclude that manipulating the mitochondrial ROS levels in oocytes may be a potential therapeutic approach to target infertility. © 2024 Federation of European Biochemical Societies.
Ann Nakai, Yuki Fukushima, Ayaka Yamamoto, Yuki Amatsu, Xiaoyan Chen, Mitsuhiro Nishigori, Yukino Yoshioka, Mari Kaneko, Takumi Koshiba, Toshio Watanabe. Increased ROS levels in mitochondrial outer membrane protein Mul1-deficient oocytes result in abnormal preimplantation embryogenesis. FEBS letters. 2024 Jul;598(14):1740-1752
PMID: 38639871
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