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4,4’-dimethoxychalcone increases resistance of mouse oocytes to postovulatory aging in vitro

  • Lu Liu
    Affiliations
    State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Suzhou Affiliated Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Nanjing, China
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  • Jie Huang
    Affiliations
    State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Suzhou Affiliated Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Nanjing, China
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  • Anlan He
    Affiliations
    State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Suzhou Affiliated Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Nanjing, China
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  • Shuai Zhou
    Affiliations
    State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Suzhou Affiliated Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Nanjing, China
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  • Qianneng Lu
    Affiliations
    State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Suzhou Affiliated Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Nanjing, China
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  • Xiaoning Yu
    Affiliations
    State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Suzhou Affiliated Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Nanjing, China
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  • Xue Bai
    Affiliations
    State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Suzhou Affiliated Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Nanjing, China
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  • Mingrui Li
    Correspondence
    Corresponding author. Mingrui Li, Tel & Fax: +86-025-86869561.
    Affiliations
    State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Suzhou Affiliated Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Nanjing, China

    Department of Clinical Nursing, School of Nursing, Nanjing Medical University, Nanjing, China
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  • Ran Huo
    Correspondence
    Ran Huo, Tel & Fax: +86-025-86869394.
    Affiliations
    State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Suzhou Affiliated Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Nanjing, China
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Published:December 08, 2021DOI:https://doi.org/10.1016/j.rbmo.2021.12.003

      ABSTRACT

      Research Question

      Does 4,4’-dimethoxychalcone (DMC), as a natural antioxidant compound, effectively improve the quality of postovulatory aging (POA) oocytes?

      Design

      Freshly ovulated metaphase II (MII) oocytes were cultured in 10μM DMC for 12h in vitro, reactive oxygen species (ROS) production, apoptosis rate, mitochondrial distribution, formation of the actin cap and fertilization and development potential of POA oocytes were studied, then we detected the change of autophagy level, and used the autophagy inhibitor 3-Methyladenine (3-MA) to prove the relationship between DMC and autophagy.

      Results

      DMC supplementation could eliminate the accumulated ROS (P<0.0001) and ROS dependent 4 hydroxynonenal (4-HNE) products (P=0.0399) to decrease apoptosis (P=0.0033), reduce the abnormal mitochondrion distribution rate (P=0.0280), improve mitochondrial membrane potential (P=0.0135) and restore the formation of the actin cap (P=0.0487), thus improved the following fertilization ability (P=0.0156) and developmental potential (P=0.0130) in POA oocytes. Furthermore, we investigated whether autophagy plays a role in the effects of DMC supplementation. The immunofluorescence results showed that POA lead to the accumulation of P62 (P=0.0083) but DMC supplementation could eliminate this accumulation (P<0.0001), the western blot result of P62 protein showed the same trend as the immunofluorescence results of POA group (P=0.0441) and DMC supplementation group (P=0.0154), and after inhibiting the autophagy by 3-MA, the DMC supplementation group could not eliminate the accumulation of ROS anymore (P=0.1704).

      Conclusions

      Our results reveal that DMC supplementation actives autophagy to protect oocytes from the postovulatory aging process, which holds promise as a feasible approach to contribute to the improvement of reproductive outcome of assisted reproductive technology (ART).

      Graphical abstract

      KEYWORDS

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      Biography

      Ran Huo, PhD, Professor of Nanjing Medical University, Deputy director of State Key Laboratory of Reproductive Medicine. She devotes herself to basic research for oogenesis, preimplantation embryo development and female infertility.
      KEY MESSAGE
      4,4’-dimethoxychalcone (DMC) improves the quality and the developmental potential of postovulatory aged (POA) oocytes. Autophagy plays a significant role in delaying the process of POA after DMC supplementation. And exogenous DMC may be potentially promising to be a feasible approach to protect oocytes from the postovulatory aging process in assisted reproductive technology.