Generic placeholder image

Current Molecular Pharmacology

Editor-in-Chief

ISSN (Print): 1874-4672
ISSN (Online): 1874-4702

General Research Article

Coenzyme Q10 Supplement Rescues Postovulatory Oocyte Aging by Regulating SIRT4 Expression

Author(s): Xupeng Xing, Jinjing Zhang, Jingcheng Zhang, Yongsheng Wang, Jingyi Wang, Jian Kang, Fusheng Quan, Jianmin Su* and Yong Zhang

Volume 15, Issue 1, 2022

Published on: 20 April, 2021

Article ID: e200421192922 Pages: 14

DOI: 10.2174/1874467214666210420112819

Price: $65

Abstract

Background: High-quality of the oocyte is crucial for embryo development and the success of human-assisted reproduction. The postovulatory aged oocytes lose developmental competence with mitochondrial dysfunction and oxidative stress. Coenzyme Q10 (CoQ10) is widely distributed in the membranes of cells and has an important role in the mitochondrial respiration chain against oxidative stress and modulation of gene expression.

Objective: The objective of this study is to investigate the functions and mechanisms of CoQ10 on delaying postovulatory oocyte aging.

Methods: Quantitative real-time PCR and Immunofluorescence staining were used to determine the expression patterns of the biogenesis genes of CoQ10 in postovulatory aged oocytes compared with fresh oocytes. The mitochondrial function, apoptosis, reactive oxygen species (ROS) accumulation and spindle abnormalities were investigated after treatment with 10 μM CoQ10 in aged groups. SIRT4 siRNA or capped RNA was injected into oocytes to investigate the function of SIRT4 on postovulatory oocyte aging and the relationship between CoQ10 and SIRT4.

Results: Multiple CoQ10 biosynthesis enzymes are insufficient, and a supplement of CoQ10 can improve oocyte quality and elevate the development competency of postovulatory aged oocytes. CoQ10 can attenuate the aging-induced abnormalities, including mitochondrial dysfunction, ROS accumulation, spindle abnormalities, and apoptosis in postovulatory aged oocytes. Furthermore, SIRT4, which was first found to be up-regulated in postovulatory aged oocytes, decreased following CoQ10 treatment. Finally, knockdown of SIRT4 can rescue aging-induced dysfunction of mitochondria, and the efficiency of CoQ10 rescuing dysfunction of mitochondria can be weakened by SIRT4 overexpression.

Conclusion: Supplement of CoQ10 protects oocytes from postovulatory aging by inhibiting SIRT4 increase.

Keywords: CoQ10, postovulatory oocyte aging, embryo development, aging-induced abnormalities, mitochondrial function, SIRT4.

Graphical Abstract

[1]
Wang, Q.; Sun, Q.Y. Evaluation of oocyte quality: Morphological, cellular and molecular predictors. Reprod. Fertil. Dev., 2007, 19(1), 1-12.
[http://dx.doi.org/10.1071/RD06103] [PMID: 17389130]
[2]
Tarín, J.J.; Pérez-Albalá, S.; Aguilar, A.; Miñarro, J.; Hermenegildo, C.; Cano, A. Long-term effects of postovulatory aging of mouse oocytes on offspring: A two-generational study. Biol. Reprod., 1999, 61(5), 1347-1355.
[http://dx.doi.org/10.1095/biolreprod61.5.1347] [PMID: 10529284]
[3]
Tarín, J.J.; Ten, J.; Vendrell, F.J.; Cano, A. Dithiothreitol prevents age-associated decrease in oocyte/conceptus viability in vitro. Hum. Reprod., 1998, 13(2), 381-386.
[http://dx.doi.org/10.1093/humrep/13.2.381] [PMID: 9557843]
[4]
Ono, T.; Mizutani, E.; Li, C.; Yamagata, K.; Wakayama, T. Offspring from intracytoplasmic sperm injection of aged mouse oocytes treated with caffeine or MG132. Genesis, 2011, 49(6), 460-471.
[http://dx.doi.org/10.1002/dvg.20756] [PMID: 21504043]
[5]
Xu, Z.; Abbott, A.; Kopf, G.S.; Schultz, R.M.; Ducibella, T. Spontaneous activation of ovulated mouse eggs: Time-dependent effects on M-phase exit, cortical granule exocytosis, maternal messenger ribonucleic acid recruitment, and inositol 1,4,5-trisphosphate sensitivity. Biol. Reprod., 1997, 57(4), 743-750.
[http://dx.doi.org/10.1095/biolreprod57.4.743] [PMID: 9314575]
[6]
Ben-Meir, A.; Burstein, E.; Borrego-Alvarez, A.; Chong, J.; Wong, E.; Yavorska, T.; Naranian, T.; Chi, M.; Wang, Y.; Bentov, Y.; Alexis, J.; Meriano, J.; Sung, H.K.; Gasser, D.L.; Moley, K.H.; Hekimi, S.; Casper, R.F.; Jurisicova, A. Coenzyme Q10 restores oocyte mitochondrial function and fertility during reproductive aging. Aging Cell, 2015, 14(5), 887-895.
[http://dx.doi.org/10.1111/acel.12368] [PMID: 26111777]
[7]
Liu, L.; Trimarchi, J.R.; Smith, P.J.; Keefe, D.L. Mitochondrial dysfunction leads to telomere attrition and genomic instability. Aging Cell, 2002, 1(1), 40-46.
[http://dx.doi.org/10.1046/j.1474-9728.2002.00004.x] [PMID: 12882352]
[8]
Zhang, T.; Zhou, Y.; Li, L.; Wang, H.H.; Ma, X.S.; Qian, W.P.; Shen, W.; Schatten, H.; Sun, Q.Y. SIRT1, 2, 3 protect mouse oocytes from postovulatory aging. Aging (Albany NY), 2016, 8(4), 685-696.
[http://dx.doi.org/10.18632/aging.100911] [PMID: 26974211]
[9]
Cui, H.; Kong, Y.; Zhang, H. Oxidative stress, mitochondrial dysfunction, and aging. J. Signal Transduct., 2012, 2012, 646354.
[http://dx.doi.org/10.1155/2012/646354] [PMID: 21977319]
[10]
Van Blerkom, J. Mitochondrial function in the human oocyte and embryo and their role in developmental competence. Mitochondrion, 2011, 11(5), 797-813.
[http://dx.doi.org/10.1016/j.mito.2010.09.012] [PMID: 20933103]
[11]
Seidler, E.A.; Moley, K.H. Metabolic determinants of mitochondrial function in oocytes. Semin. Reprod. Med., 2015, 33(6), 396-400.
[http://dx.doi.org/10.1055/s-0035-1567822] [PMID: 26562288]
[12]
Kawamukai, M. Biosynthesis and bioproduction of coenzyme Q10 by yeasts and other organisms. Biotechnol. Appl. Biochem., 2009, 53(Pt 4), 217-226.
[http://dx.doi.org/10.1042/BA20090035] [PMID: 19531029]
[13]
Barcelos, I.P.; Haas, R.H. CoQ10 and Aging. Biology (Basel), 2019, 8(2), E28.
[http://dx.doi.org/10.3390/biology8020028] [PMID: 31083534]
[14]
Brea-Calvo, G.; Rodríguez-Hernández, A.; Fernández-Ayala, D.J.; Navas, P.; Sánchez-Alcázar, J.A. Chemotherapy induces an increase in coenzyme Q10 levels in cancer cell lines. Free Radic. Biol. Med., 2006, 40(8), 1293-1302.
[http://dx.doi.org/10.1016/j.freeradbiomed.2005.11.014] [PMID: 16631519]
[15]
Groneberg, D.A.; Kindermann, B.; Althammer, M.; Klapper, M.; Vormann, J.; Littarru, G.P.; Döring, F. Coenzyme Q10 affects expression of genes involved in cell signalling, metabolism and transport in human CaCo-2 cells. Int. J. Biochem. Cell Biol., 2005, 37(6), 1208-1218.
[http://dx.doi.org/10.1016/j.biocel.2004.11.017] [PMID: 15778085]
[16]
Schmelzer, C.; Kitano, M.; Hosoe, K.; Döring, F. Ubiquinol affects the expression of genes involved in PPARα signalling and lipid metabolism without changes in methylation of CpG promoter islands in the liver of mice. J. Clin. Biochem. Nutr., 2012, 50(2), 119-126.
[http://dx.doi.org/10.3164/jcbn.11-19] [PMID: 22448092]
[17]
Tran, U.C.; Clarke, C.F. Endogenous synthesis of coenzyme Q in eukaryotes. Mitochondrion, 2007, 7(Suppl.), S62-S71.
[http://dx.doi.org/10.1016/j.mito.2007.03.007] [PMID: 17482885]
[18]
Hayashi, K.; Ogiyama, Y.; Yokomi, K.; Nakagawa, T.; Kaino, T.; Kawamukai, M. Functional conservation of coenzyme Q biosynthetic genes among yeasts, plants, and humans. PLoS One, 2014, 9(6), e99038.
[http://dx.doi.org/10.1371/journal.pone.0099038] [PMID: 24911838]
[19]
Quinzii, C.; Naini, A.; Salviati, L.; Trevisson, E.; Navas, P.; Dimauro, S.; Hirano, M. A mutation in para-hydroxybenzoate-polyprenyl transferase (COQ2) causes primary coenzyme Q10 deficiency. Am. J. Hum. Genet., 2006, 78(2), 345-349.
[http://dx.doi.org/10.1086/500092] [PMID: 16400613]
[20]
Nguyen, T.P.; Casarin, A.; Desbats, M.A.; Doimo, M.; Trevisson, E.; Santos-Ocaña, C.; Navas, P.; Clarke, C.F.; Salviati, L. Molecular characterization of the human COQ5 C-methyltransferase in coenzyme Q10 biosynthesis. Biochim. Biophys. Acta, 2014, 1841(11), 1628-1638.
[http://dx.doi.org/10.1016/j.bbalip.2014.08.007] [PMID: 25152161]
[21]
Yen, H.C.; Liu, Y.C.; Kan, C.C.; Wei, H.J.; Lee, S.H.; Wei, Y.H.; Feng, Y.H.; Chen, C.W.; Huang, C.C. Disruption of the human COQ5-containing protein complex is associated with diminished coenzyme Q10 levels under two different conditions of mitochondrial energy deficiency. Biochim. Biophys. Acta, 2016, 1860(9), 1864-1876.
[http://dx.doi.org/10.1016/j.bbagen.2016.05.005] [PMID: 27155576]
[22]
Nakai, D.; Yuasa, S.; Takahashi, M.; Shimizu, T.; Asaumi, S.; Isono, K.; Takao, T.; Suzuki, Y.; Kuroyanagi, H.; Hirokawa, K.; Koseki, H.; Shirsawa, T. Mouse homologue of coq7/clk-1, longevity gene in Caenorhabditis elegans, is essential for coenzyme Q synthesis, maintenance of mitochondrial integrity, and neurogenesis. Biochem. Biophys. Res. Commun., 2001, 289(2), 463-471.
[http://dx.doi.org/10.1006/bbrc.2001.5977] [PMID: 11716496]
[23]
Zhang, M.; ShiYang, X.; Zhang, Y.; Miao, Y.; Chen, Y.; Cui, Z.; Xiong, B. Coenzyme Q10 ameliorates the quality of postovulatory aged oocytes by suppressing DNA damage and apoptosis. Free Radic. Biol. Med., 2019, 143, 84-94.
[http://dx.doi.org/10.1016/j.freeradbiomed.2019.08.002] [PMID: 31398498]
[24]
Sun, Y.L.; Tang, S.B.; Shen, W.; Yin, S.; Sun, Q.Y. Roles of resveratrol in improving the quality of postovulatory aging oocytes in vitro. Cells, 2019, 8(10), E1132.
[http://dx.doi.org/10.3390/cells8101132] [PMID: 31547622]
[25]
Zeng, J.; Jiang, M.; Wu, X.; Diao, F.; Qiu, D.; Hou, X.; Wang, H.; Li, L.; Li, C.; Ge, J.; Liu, J.; Ou, X.; Wang, Q. SIRT4 is essential for metabolic control and meiotic structure during mouse oocyte maturation. Aging Cell, 2018, 17(4), e12789.
[http://dx.doi.org/10.1111/acel.12789] [PMID: 29845740]
[26]
Jeong, S.M.; Xiao, C.; Finley, L.W.; Lahusen, T.; Souza, A.L.; Pierce, K.; Li, Y.H.; Wang, X.; Laurent, G.; German, N.J.; Xu, X.; Li, C.; Wang, R.H.; Lee, J.; Csibi, A.; Cerione, R.; Blenis, J.; Clish, C.B.; Kimmelman, A.; Deng, C.X.; Haigis, M.C. SIRT4 has tumor-suppressive activity and regulates the cellular metabolic response to DNA damage by inhibiting mitochondrial glutamine metabolism. Cancer Cell, 2013, 23(4), 450-463.
[http://dx.doi.org/10.1016/j.ccr.2013.02.024] [PMID: 23562301]
[27]
Ho, L.; Titus, A.S.; Banerjee, K.K.; George, S.; Lin, W.; Deota, S.; Saha, A.K.; Nakamura, K.; Gut, P.; Verdin, E.; Kolthur-Seetharam, U. SIRT4 regulates ATP homeostasis and mediates a retrograde signaling via AMPK. Aging (Albany NY), 2013, 5(11), 835-849.
[http://dx.doi.org/10.18632/aging.100616] [PMID: 24296486]
[28]
Lang, A.; Anand, R.; Altinoluk-Hambüchen, S.; Ezzahoini, H.; Stefanski, A.; Iram, A.; Bergmann, L.; Urbach, J.; Böhler, P.; Hänsel, J.; Franke, M.; Stühler, K.; Krutmann, J.; Scheller, J.; Stork, B.; Reichert, A.S.; Piekorz, R.P. SIRT4 interacts with OPA1 and regulates mitochondrial quality control and mitophagy. Aging (Albany NY), 2017, 9(10), 2163-2189.
[http://dx.doi.org/10.18632/aging.101307] [PMID: 29081403]
[29]
Persson, E.M.; Gustafsson, A.S.; Carlsson, A.S.; Nilsson, R.G.; Knutson, L.; Forsell, P.; Hanisch, G.; Lennernäs, H.; Abrahamsson, B. The effects of food on the dissolution of poorly soluble drugs in human and in model small intestinal fluids. Pharm. Res., 2005, 22(12), 2141-2151.
[http://dx.doi.org/10.1007/s11095-005-8192-x] [PMID: 16247711]
[30]
Sun, H.; Kang, J.; Su, J.; Zhang, J.; Zhang, L.; Liu, X.; Zhang, J.; Wang, F.; Lu, Z.; Xing, X.; Chen, H.; Zhang, Y. Methionine adenosyltransferase 2A regulates mouse zygotic genome activation and morula to blastocyst transition. Biol. Reprod., 2019, 100(3), 601-617.
[http://dx.doi.org/10.1093/biolre/ioy194] [PMID: 30265288]
[31]
Cheng, Y.; Zhang, J.; Wu, T.; Jiang, X.; Jia, H.; Qing, S.; An, Q.; Zhang, Y.; Su, J. Reproductive toxicity of acute Cd exposure in mouse: Resulting in oocyte defects and decreased female fertility. Toxicol. Appl. Pharmacol., 2019, 379, 114684.
[http://dx.doi.org/10.1016/j.taap.2019.114684] [PMID: 31325558]
[32]
Xu, D.; Jiang, X.; He, H.; Liu, D.; Yang, L.; Chen, H.; Wu, L.; Geng, G.; Li, Q. SIRT2 functions in aging, autophagy, and apoptosis in post-maturation bovine oocytes. Life Sci., 2019, 232, 116639.
[http://dx.doi.org/10.1016/j.lfs.2019.116639] [PMID: 31295472]
[33]
Doimo, M.; Trevisson, E.; Airik, R.; Bergdoll, M.; Santos-Ocaña, C.; Hildebrandt, F.; Navas, P.; Pierrel, F.; Salviati, L. Effect of vanillic acid on COQ6 mutants identified in patients with coenzyme Q10 deficiency. Biochim. Biophys. Acta, 2014, 1842(1), 1-6.
[http://dx.doi.org/10.1016/j.bbadis.2013.10.007] [PMID: 24140869]
[34]
Wang, H.; Jo, Y.J.; Oh, J.S.; Kim, N.H. Quercetin delays postovulatory aging of mouse oocytes by regulating SIRT expression and MPF activity. Oncotarget, 2017, 8(24), 38631-38641.
[http://dx.doi.org/10.18632/oncotarget.16219] [PMID: 28418847]
[35]
Jeon, H.J.; Cui, X.S.; Guo, J.; Lee, J.M.; Kim, J.S.; Oh, J.S. TCTP regulates spindle assembly during postovulatory aging and prevents deterioration in mouse oocyte quality. Biochim. Biophys. Acta Mol. Cell Res., 2017, 1864(7), 1328-1334.
[http://dx.doi.org/10.1016/j.bbamcr.2017.05.002] [PMID: 28476647]
[36]
Zhang, X.; Liu, X.; Chen, L.; Wu, D.Y.; Nie, Z.W.; Gao, Y.Y.; Miao, Y.L. Caffeine delays oocyte aging and maintains the quality of aged oocytes safely in mouse. Oncotarget, 2017, 8(13), 20602-20611.
[http://dx.doi.org/10.18632/oncotarget.15292] [PMID: 28206974]
[37]
Yang, Q.; Dai, S.; Luo, X.; Zhu, J.; Li, F.; Liu, J.; Yao, G.; Sun, Y. Melatonin attenuates postovulatory oocyte dysfunction by regulating SIRT1 expression. Reproduction, 2018, 156(1), 81-92.
[http://dx.doi.org/10.1530/REP-18-0211] [PMID: 29752296]
[38]
Bentov, Y.; Casper, R.F. The aging oocyte- can mitochondrial function be improved? Fertil. Steril., 2013, 99(1), 18-22.
[http://dx.doi.org/10.1016/j.fertnstert.2012.11.031] [PMID: 23273985]
[39]
Desbats, M.A.; Morbidoni, V.; Silic-Benussi, M.; Doimo, M.; Ciminale, V.; Cassina, M.; Sacconi, S.; Hirano, M.; Basso, G.; Pierrel, F.; Navas, P.; Salviati, L.; Trevisson, E. The COQ2 genotype predicts the severity of coenzyme Q10 deficiency. Hum. Mol. Genet., 2016, 25(19), 4256-4265.
[http://dx.doi.org/10.1093/hmg/ddw257] [PMID: 27493029]
[40]
Reynier, P.; May-Panloup, P.; Chrétien, M.F.; Morgan, C.J.; Jean, M.; Savagner, F.; Barrière, P.; Malthièry, Y. Mitochondrial DNA content affects the fertilizability of human oocytes. Mol. Hum. Reprod., 2001, 7(5), 425-429.
[http://dx.doi.org/10.1093/molehr/7.5.425] [PMID: 11331664]
[41]
Hernández-Camacho, J.D.; Bernier, M.; López-Lluch, G.; Navas, P. Coenzyme Q10 supplementation in aging and disease. Front. Physiol., 2018, 9, 44.
[http://dx.doi.org/10.3389/fphys.2018.00044] [PMID: 29459830]
[42]
Quinzii, C.M.; López, L.C.; Von-Moltke, J.; Naini, A.; Krishna, S.; Schuelke, M.; Salviati, L.; Navas, P.; DiMauro, S.; Hirano, M. Respiratory chain dysfunction and oxidative stress correlate with severity of primary CoQ10 deficiency. FASEB J., 2008, 22(6), 1874-1885.
[http://dx.doi.org/10.1096/fj.07-100149] [PMID: 18230681]
[43]
Xia, M.; He, H.; Wang, Y.; Liu, M.; Zhou, T.; Lin, M.; Zhou, Z.; Huo, R.; Zhou, Q.; Sha, J. PCBP1 is required for maintenance of the transcriptionally silent state in fully grown mouse oocytes. Cell Cycle, 2012, 11(15), 2833-2842.
[http://dx.doi.org/10.4161/cc.21169] [PMID: 22801551]
[44]
Borsuk, E.; Milik, E. Fully grown mouse oocyte contains transcription inhibiting activity which acts through histone deacetylation. Mol. Reprod. Dev., 2005, 71(4), 509-515.
[http://dx.doi.org/10.1002/mrd.20300] [PMID: 15858797]
[45]
Huang, J.C.; Yan, L.Y.; Lei, Z.L.; Miao, Y.L.; Shi, L.H.; Yang, J.W.; Wang, Q.; Ouyang, Y.C.; Sun, Q.Y.; Chen, D.Y. Changes in histone acetylation during postovulatory aging of mouse oocyte. Biol. Reprod., 2007, 77(4), 666-670.
[http://dx.doi.org/10.1095/biolreprod.107.062703] [PMID: 17582009]
[46]
Mahmoud, A.R.; Ali, F.E.M.; Abd-Elhamid, T.H.; Hassanein, E.H.M. Coenzyme Q10 protects hepatocytes from ischemia reperfusion-induced apoptosis and oxidative stress via regulation of Bax/Bcl-2/PUMA and Nrf-2/FOXO-3/Sirt-1 signaling pathways. Tissue Cell, 2019, 60, 1-13.
[http://dx.doi.org/10.1016/j.tice.2019.07.007] [PMID: 31582012]
[47]
Miao, Y.L.; Kikuchi, K.; Sun, Q.Y.; Schatten, H. Oocyte aging: Cellular and molecular changes, developmental potential and reversal possibility. Hum. Reprod. Update, 2009, 15(5), 573-585.
[http://dx.doi.org/10.1093/humupd/dmp014] [PMID: 19429634]
[48]
Lord, T.; Nixon, B.; Jones, K.T.; Aitken, R.J. Melatonin prevents postovulatory oocyte aging in the mouse and extends the window for optimal fertilization in vitro. Biol. Reprod., 2013, 88(3), 67.
[http://dx.doi.org/10.1095/biolreprod.112.106450] [PMID: 23365415]
[49]
Goud, A.P.; Goud, P.T.; Diamond, M.P.; Abu-Soud, H.M. Nitric oxide delays oocyte aging. Biochemistry, 2005, 44(34), 11361-11368.
[http://dx.doi.org/10.1021/bi050711f] [PMID: 16114873]
[50]
Dai, X.; Lu, Y.; Zhang, M.; Miao, Y.; Zhou, C.; Cui, Z.; Xiong, B. Melatonin improves the fertilization ability of post-ovulatory aged mouse oocytes by stabilizing ovastacin and Juno to promote sperm binding and fusion. Hum. Reprod., 2017, 32(3), 598-606.
[http://dx.doi.org/10.1093/humrep/dew362] [PMID: 28137755]
[51]
Bermejo-Martin, J.F.; Martín-Fernandez, M.; López-Mestanza, C.; Duque, P.; Almansa, R. shared features of endothelial dysfunction between sepsis and its preceding risk factors (aging and chronic disease). J. Clin. Med., 2018, 7(11), E400.
[http://dx.doi.org/10.3390/jcm7110400] [PMID: 30380785]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy