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

Tijdschriftbijdrage - Tijdschriftartikel

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 mu M each) during bovine oocyte IVM. Then, we tested the protective capacity of MitoQ (0.1 mu M) against palmitic acid (PA)-induced lipotoxicity and mitochondrial dysfunction in oocytes.Results Exposure to MitoQ, or TPP only, at 1 mu M 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 mu M MitoQ. In contrast, 0.1 mu M 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.
Tijdschrift: Journal of assisted reproduction and genetics
ISSN: 1058-0468
Volume: 41
Pagina's: 371 - 383
Jaar van publicatie:2024
Trefwoorden:A1 Journal article
Toegankelijkheid:Embargoed