Increased ROS levels in mitochondrial outer membrane protein Mul1 ‐deficient oocytes result in abnormal preimplantation embryogenesis

We found that female Mul1-deficient mice are infertile and their oocytes contain high reactive oxygen species (ROS) concentrations. After fertilization, Mul1-deficient embryos showed a DNA damage response (DDR) and abnormal preimplantation embryogenesis, which was rescued byN-acetyl-l-cysteine 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. Reactive oxygen species (ROS) are associated with oocyte maturation inhibition, andN-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 increas es 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.

Source: FEBS Letters - April 20, 2024 Category: Biochemistry Authors: Ann Nakai, Yuki Fukushima, Ayaka Yamamoto, Yuki Amatsu, Xiaoyan Chen, Mitsuhiro Nishigori, Yukino Yoshioka, Mari Kaneko, Takumi Koshiba, Toshio Watanabe Tags: Research Letter Source Type: research