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26-12-2023 | Gamete Biology

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

Authors: Waleed F.A. Marei, Omnia Mohey-Elsaeed, Isabel Pintelon, Jo L.M.R. Leroy

Published in: Journal of Assisted Reproduction and Genetics | Issue 2/2024

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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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Metadata
Title
Risks of using mitoquinone during in vitro maturation and its potential protective effects against lipotoxicity-induced oocyte mitochondrial stress
Authors
Waleed F.A. Marei
Omnia Mohey-Elsaeed
Isabel Pintelon
Jo L.M.R. Leroy
Publication date
26-12-2023
Publisher
Springer US
Published in
Journal of Assisted Reproduction and Genetics / Issue 2/2024
Print ISSN: 1058-0468
Electronic ISSN: 1573-7330
DOI
https://doi.org/10.1007/s10815-023-02994-7

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