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Low MFN2 expression related to ageing in granulosa cells is associated with assisted reproductive technology outcome

  • Author Footnotes
    These authors contributed equally to this work.
    Lingjuan Wang
    Footnotes
    † These authors contributed equally to this work.
    Affiliations
    Family Planning Research Institute, Tongji Medical College, Huazhong University of Science and Technology, China

    Centre of Reproductive Medicine, Tongji Medical College, Huazhong University of Science and Technology, China
    Search for articles by this author
  • Author Footnotes
    These authors contributed equally to this work.
    Su Song
    Footnotes
    † These authors contributed equally to this work.
    Affiliations
    Centre of Reproductive Medicine, Tongji Medical College, Huazhong University of Science and Technology, China
    Search for articles by this author
  • Xuemei Liu
    Affiliations
    Reproductive Medicine Centre, Yantai Yuhuangding Hospital of Qingdao University, China
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  • Mengdi Zhang
    Affiliations
    Family Planning Research Institute, Tongji Medical College, Huazhong University of Science and Technology, China

    Centre of Reproductive Medicine, Tongji Medical College, Huazhong University of Science and Technology, China
    Search for articles by this author
  • Wenpei Xiang
    Correspondence
    Corresponding author.
    Affiliations
    Family Planning Research Institute, Tongji Medical College, Huazhong University of Science and Technology, China

    Centre of Reproductive Medicine, Tongji Medical College, Huazhong University of Science and Technology, China
    Search for articles by this author
  • Author Footnotes
    These authors contributed equally to this work.
Published:December 14, 2018DOI:https://doi.org/10.1016/j.rbmo.2018.10.011

      Abstract

      Research question

      Is low MFN2 expression associated with ageing in granulosa cells as well as assisted reproductive technology (ART) outcome, and what is the underlying mechanism of action of MFN2?

      Design

      In a prospective study, fresh granulosa cells were obtained from 161 women aged 20–40 years who underwent IVF with embryo transfer and who were divided into two groups: the diminished ovarian reserve (DOR) group (n = 51) and the control group (n = 110). Patient characteristics including age, infertility duration, body mass index, FSH, anti-Müllerian hormone (AMH), antral follicle count (AFC) and husband's semen parameters and granulosa cell MFN2 expression levels, cell apoptosis, mitochondrial membrane potential (ΔΨm) and ATP levels were analysed.

      Results

      There were no significant differences between the DOR and control groups in terms of age, infertility duration and husband’’ semen parameters; however, significant (P< 0.05) changes were found between the two groups in FSH, AMH and AFC levels. MFN2 expression was remarkably lower in granulosa cells from the DOR group and decreased in both groups as age increased. Furthermore, among young patients, MFN2 levels significantly increased in patients with pregnancy. MFN2 protein levels and cell apoptosis were lower in the MFN2 knockdown (MFN2-siRNA) group than in the control (Cy3-siRNA) group. ΔΨm and ATP levels were reduced in the MFN2-siRNA group compared with the Cy3-siRNA group.

      Conclusions

      Low MFN2 expression levels in granulosa cells were related to ageing, which may be involved in the clinical outcome of ART by promoting cell apoptosis and affecting mitochondrial function.

      Keywords

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      Biography

      Wenpei Xiang is Professor of Reproductive Medicine at the Family Planning Research Institute. She focuses on oogenesis, POF and female reproductive endocrinology. Her team tries to address the effect and mechanism of mitofusin 2 (MFN2) on oogenesis and explore the pathogenesis of premature ovarian failure.
      Key message
      MFN2 expression decreased with age, which may be related to assisted reproductive technology treatment outcome by promoting cell apoptosis and affecting mitochondrial function. Oocyte quality and embryonic development could be regulated by the MFN2/mitochondrial pathway.