PMID- 38146030 OWN - NLM STAT- MEDLINE DCOM- 20240227 LR - 20240306 IS - 1573-7330 (Electronic) IS - 1058-0468 (Print) IS - 1058-0468 (Linking) VI - 41 IP - 2 DP - 2024 Feb TI - Risks of using mitoquinone during in vitro maturation and its potential protective effects against lipotoxicity-induced oocyte mitochondrial stress. PG - 371-383 LID - 10.1007/s10815-023-02994-7 [doi] AB - 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 muM each) during bovine oocyte IVM. Then, we tested the protective capacity of MitoQ (0.1 muM) against palmitic acid (PA)-induced lipotoxicity and mitochondrial dysfunction in oocytes. RESULTS: Exposure to MitoQ, or TPP only, at 1 muM 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 muM MitoQ. In contrast, 0.1 muM 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. CI - (c) 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature. FAU - Marei, Waleed F A AU - Marei WFA AUID- ORCID: 0000-0002-8498-8903 AD - Gamete Research Centre, Department of Veterinary Sciences, University of Antwerp, Antwerp, Belgium. waleed.marei@uantwerpen.be. AD - Department of Theriogenology, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt. waleed.marei@uantwerpen.be. FAU - Mohey-Elsaeed, Omnia AU - Mohey-Elsaeed O AD - Department of Histology and Cytology, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt. AD - Laboratory of Cell Biology and Histology, University of Antwerp, Antwerp, Belgium. FAU - Pintelon, Isabel AU - Pintelon I AD - Laboratory of Cell Biology and Histology, University of Antwerp, Antwerp, Belgium. FAU - Leroy, Jo L M R AU - Leroy JLMR AD - Gamete Research Centre, Department of Veterinary Sciences, University of Antwerp, Antwerp, Belgium. LA - eng GR - R01 OH004216/OH/NIOSH CDC HHS/United States PT - Journal Article DEP - 20231226 PL - Netherlands TA - J Assist Reprod Genet JT - Journal of assisted reproduction and genetics JID - 9206495 RN - 47BYS17IY0 (mitoquinone) RN - 0 (Organophosphorus Compounds) RN - 1339-63-5 (Ubiquinone) SB - IM MH - Humans MH - Animals MH - Cattle MH - *In Vitro Oocyte Maturation Techniques/methods MH - Oocytes MH - Blastocyst/metabolism MH - Embryonic Development MH - Mitochondria/metabolism MH - *Mitochondrial Diseases MH - *Organophosphorus Compounds MH - Ubiquinone/*analogs & derivatives PMC - PMC10894804 OTO - NOTNLM OT - CoQ10 OT - Embryo OT - IVF OT - MitoQ OT - Obesity OT - Oocyte OT - Oxidative stress COIS- The authors declare no competing interests. EDAT- 2023/12/26 00:42 MHDA- 2024/02/27 06:45 PMCR- 2025/02/01 CRDT- 2023/12/25 23:22 PHST- 2023/07/13 00:00 [received] PHST- 2023/11/17 00:00 [accepted] PHST- 2025/02/01 00:00 [pmc-release] PHST- 2024/02/27 06:45 [medline] PHST- 2023/12/26 00:42 [pubmed] PHST- 2023/12/25 23:22 [entrez] AID - 10.1007/s10815-023-02994-7 [pii] AID - 2994 [pii] AID - 10.1007/s10815-023-02994-7 [doi] PST - ppublish SO - J Assist Reprod Genet. 2024 Feb;41(2):371-383. doi: 10.1007/s10815-023-02994-7. Epub 2023 Dec 26.