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Risks of using mitoquinone during in vitro maturation and its potential protective effects against lipotoxicity-induced oocyte mitochondrial stress

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

Abstract

Purpose

Oxidative stress and mitochondrial dysfunction play central roles in reduced oocyte quality and infertility in obese patients. Mitochondria-targeted treatments containing co-enzyme Q10 such as mitoquinone (MitoQ) can increase mitochondrial antioxidative capacity; however, their safety and efficiency when supplemented to oocytes under lipotoxic conditions have not been described.

Methods

We tested the effect of different concentrations of MitoQ or its cationic carrier (TPP) (0, 0.1, 0.5, 1.0 μM each) during bovine oocyte IVM. Then, we tested the protective capacity of MitoQ (0.1 μM) against palmitic acid (PA)–induced lipotoxicity and mitochondrial dysfunction in oocytes.

Results

Exposure to MitoQ, or TPP only, at 1 μM significantly (P<0.05) reduced oocyte mitochondrial inner membrane potential (JC-1 staining) and resulted in reduced cleavage and blastocyst rates compared with solvent control. Lower concentrations of MitoQ or TPP had no effects on embryo development under control (PA-free) conditions. As expected, PA increased the levels of MMP and ROS in oocytes (CellROX staining) and reduced cleavage and blastocyst rates compared with the controls (P<0.05). These negative effects were ameliorated by 0.1 μM MitoQ. In contrast, 0.1 μM TPP alone had no protective effects. MitoQ also normalized the expression of HSP10 and TFAM, and partially normalized HSP60 in the produced blastocysts, indicating at least a partial alleviation of PA-induced mitochondrial stress.

Conclusion

Oocyte exposure to MitoQ may disturb mitochondrial bioenergetic functions and developmental capacity due to a TPP-induced cationic overload. A fine-tuned concentration of MitoQ can protect against lipotoxicity-induced mitochondrial stress during IVM and restore developmental competence and embryo quality.

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Data availability

Raw data files are available at Marei, Waleed (2023), “MitoQ during IVM”, Mendeley Data, V1, doi: 10.17632/htrsvbjfk5.1.

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Acknowledgements

The authors would like to acknowledge ACAM, the microscopy core facility of the University of Antwerp, for the use of their microscopy facilities. The Leica SP8 microscope used in this publication was funded by a Medium-scale research infrastructure grant (GOH4216N) of the FWO.

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Authors and Affiliations

  1. Gamete Research Centre, Department of Veterinary Sciences, University of Antwerp, Antwerp, Belgium

    Waleed F.A. Marei & Jo L.M.R. Leroy

  2. Department of Theriogenology, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt

    Waleed F.A. Marei

  3. Department of Histology and Cytology, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt

    Omnia Mohey-Elsaeed

  4. Laboratory of Cell Biology and Histology, University of Antwerp, Antwerp, Belgium

    Omnia Mohey-Elsaeed & Isabel Pintelon

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  1. Waleed F.A. Marei
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Contributions

WFAM contributed with the main project idea, conducted the experiments, analyzed the data, and wrote the manuscript. O.M-E performed the confocal microscopy and image analysis. IP helped with the optimization of microscopy and image data analysis. J.L.M.R supervised the project and critically read and edited the manuscript.

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Correspondence to Waleed F.A. Marei.

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Marei, W.F., Mohey-Elsaeed, O., Pintelon, I. et al. Risks of using mitoquinone during in vitro maturation and its potential protective effects against lipotoxicity-induced oocyte mitochondrial stress. J Assist Reprod Genet 41, 371–383 (2024). https://doi.org/10.1007/s10815-023-02994-7

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  • DOI: https://doi.org/10.1007/s10815-023-02994-7

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