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Mitochondrial oxygen consumption rate of human embryos declines with maternal age

  • Embryo Biology
  • Published:
Journal of Assisted Reproduction and Genetics Aims and scope Submit manuscript

Abstract

Purpose

The fertility of women decreases with age because of factors such as an increased incidence of aneuploidies and—possibly—decreased mitochondrial activity in oocytes. However, the relationship between maternal aging and mitochondrial function of their embryos remains unknown. Here, we assessed the relationship between maternal age and mitochondrial functions in their oocytes and embryos

Methods

The relationships between maternal age and oxygen consumption rates (OCRs), mitochondrial DNA (mtDNA) copy numbers, or blastocyst development was investigated using 81 embryos donated from 63 infertility couples. The developmental rates from morulae to blastocysts were retrospectively analyzed using data of 105 patients.

Results

The OCRs of morulae decreased with maternal age (r2 = 0.48, P < 0.05) although there were no relationships between maternal age and mtDNA copy number in any stages. The more oxygen consumed at the morula stage, the shorter time was required for embryo development to the mid-stage blastocyst (r2 = 0.236, P < 0.05). According to the clinical data analysis, the developmental rate from morulae to blastocysts decreased with maternal age (P < 0.05, < 37 years, 81.1%, vs. ≥ 37 years, 64.1%).

Conclusions

The data of the present study revealed that mitochondrial function at the morula stage of human embryos decreased with their maternal age and a decrease of mitochondrial function led to slow-paced development and impaired developmental rate from morulae to blastocysts.

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Acknowledgments

The authors thank Drs. M. Inoue, G. Udayanga, A. Takeshita, and T. Yamochi for their helpful comments, and James Cummins, PhD, from EDANZ Group (www.edanzediting.com/ac) for editing a draft of this manuscript.

Authors’ roles

N.M. and S.H. designed the experiment, interpreted the results, and wrote the manuscript with help from all authors. M.Y. measured OCRs. T.N., M.S., and Y.N. were involved in the analysis of clinical data. H.I. designed the qPCR procedures. A.F., H.S., and Y.M. supervised the project.

Funding

Part of this work was supported by a grant from the Japan Agency for Medical Research and Development (17gk0110014h0002 and 18gk0110014h0003 to S.H. and Y.M.), and a grant from the Japan Society for the Promotion of Science (KAKENHI 17K08144 and 20K09674 to S.H.).

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Authors and Affiliations

  1. IVF Namba Clinic, Osaka, 550-0015, Japan

    Naoharu Morimoto, Masaya Yamanaka, Tatsuya Nakano, Manabu Satoh & Yoshiharu Nakaoka

  2. Reproductive Science, Graduate School of Medicine, Osaka City University, Osaka, 545-8585, Japan

    Naoharu Morimoto & Shu Hashimoto

  3. Department of Obstetrics and Gynecology, Hyogo College of Medicine, Nishinomiya, Hyogo, 663-8501, Japan

    Naoharu Morimoto, Atsushi Fukui & Hiroaki Shibahara

  4. Department of Animal Science, Tokyo University of Agriculture, Kanagawa, 243-0034, Japan

    Hisataka Iwata

  5. HORAC Grand Front Osaka Clinic, Osaka, 530-0011, Japan

    Yoshiharu Morimoto

Authors
  1. Naoharu Morimoto
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  2. Shu Hashimoto
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  3. Masaya Yamanaka
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  8. Atsushi Fukui
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  9. Yoshiharu Morimoto
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Corresponding author

Correspondence to Shu Hashimoto.

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The authors declare that they no conflict of interest exists.

Ethical approval

The study was performed in accordance with Declaration of Helsinki protocols 7th version. This study was approved by the local ethics Institutional Review Board of IVF Namba Clinic, the institutional review board of Hyogo College of Medicine, and the Japan Society of Obstetrics and Gynecology (Registry Nos 135 and 138).

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Morimoto, N., Hashimoto, S., Yamanaka, M. et al. Mitochondrial oxygen consumption rate of human embryos declines with maternal age. J Assist Reprod Genet 37, 1815–1821 (2020). https://doi.org/10.1007/s10815-020-01869-5

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  • DOI: https://doi.org/10.1007/s10815-020-01869-5

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