DOI QR코드

DOI QR Code

Pyrroloquinoline quinone promotes porcine oocyte in vitro maturation and subsequent embryo development by enhancing lipid metabolism and improving mitochondrial function

  • Zehua Zhang (College of Animal Science and Technology, Inner Mongolia Minzu University) ;
  • Zhigang Gao (College of Animal Science and Technology, Inner Mongolia Minzu University) ;
  • Zhenwei Jia (College of Animal Science and Technology, Inner Mongolia Minzu University)
  • 투고 : 2024.12.03
  • 심사 : 2025.03.03
  • 발행 : 2025.08.01

초록

Objective: The present study evaluated the beneficial effects of pyrroloquinoline quinone (PQQ) on in vitro maturation (IVM) of porcine oocyte and subsequent early embryo development. Methods: Porcine cumulus oocyte complexes were cultured in IVM medium with supplementation of 0, 200, 400, 800 or 1600 nM PQQ for 42 h. We first examined cumulus expansion index (CEI) and the rate of oocyte nuclear maturation. Then, we assessed oocyte mitochondrial function, oxidative stress levels, lipid metabolism and subsequent embryonic development. Results: PQQ (800 nM) supplementation significantly increased CEI and the nuclear maturation rate of oocytes following IVM. Additionally, oocysts supplemented with 800 nM of PQQ showed significantly increased mitochondrial content, mitochondrial membrane potential, activity, and mRNA expression levels of genes associated with mitochondrial biogenesis (PGC-1a, NRF1, NRF2 and TFAM). PQQ significantly reduced the levels of reactive oxygen species, lipid drop-lets, and fatty acids content, while enhancing the mRNA expression levels of genes related to antioxidant activity (SOD1, SOD2, GPX and CAT), lipolysis (ATGL and HSL) and β-oxidation (CPT1B and CPT2) in porcine oocytes. PQQ (800 nM) supplementation significantly increased cleavage rate, blastocyst formation rate, and total blastocyst cell numbers following partheno-genetic activation. Conclusion: PQQ supplementation during IVM positively influences porcine oocyte maturation and subse-quent embryonic development by enhancing mitochondrial function and lipid metabolism and alleviating oxidative stress.

키워드

과제정보

This work was supported by the Natural Science Foundation of Inner Mongolia Autonomous Region of China (2022LHMS03018, 2023MS03005), and the National Natural Science Foundation of China (32360835).

참고문헌

  1. Gilchrist RB, Thompson JG. Oocyte maturation: emerging concepts and technologies to improve developmental potential in vitro. Theriogenology 2007;67:6-15. https://doi.org/10.1016/j.theriogenology.2006.09.027
  2. Kirillova A, Smitz JEJ, Sukhikh GT, Mazunin I. The role of mitochondria in oocyte matu-ration. Cells 2021;10:2484. https://doi.org/10.3390/cells10092484
  3. Al-Zubaidi U, Adhikari D, Cinar O, et al. Mitochondria targeted therapeutics, MitoQ and BGP-15, reverse aging associated meiotic spindle defects in mouse and human oocytes. Hum Reprod 2021;36:771-84. https://doi.org/10.1093/humrep/deaa300
  4. Rao A, Satheesh A, Nayak G, et al. High-fat diet leads to elevated lipid accumulation and endoplasmic reticulum stress in oocytes, causing poor embryo development. Reprod Fertil Dev 2020;32:1169-79. https://doi.org/10.1071/RD20112
  5. Dunning KR, Robker RL. Promoting lipid utilization with l-carnitine to improve oocyte quality. Anim Reprod Sci 2012;134:69-75. https://doi.org/10.1016/j.anireprosci.2012.08.013
  6. Khan R, Jiang X, Hameed U, Shi Q. Role of lipid metabolism and signaling in mammalian oocyte maturation, quality, and acquisition of competence. Front Cell Dev Biol 2021;9:639704. https://doi.org/10.3389/fcell.2021.639704
  7. Akagawa M, Nakano M, Ikemoto K. Recent progress in studies on the health benefits of pyrroloquinoline quinone. Biosci Biotechnol Biochem 2016;80:13-22. https://doi.org/10.1080/09168451.2015.1062715
  8. Ikemoto K, Mori S, Mukai K. Synthesis and crystal structure of pyrroloquinoline quinol (PQQH2) and pyrroloquinoline quinone (PQQ). Acta Crystallogr B Struct Sci Cryst Eng Mater 2017;73:489-97. https://doi.org/10.1107/S205252061
  9. Chowanadisai W, Bauerly KA, Tchaparian E, Wong A, Cortopassi GA, Rucker RB. Pyrrol-oquinoline quinone stimulates mitochondrial biogenesis through cAMP response ele-ment-binding protein phosphorylation and increased PGC-1α expression. J Biol Chem 2010;285:142-52. https://doi.org/10.1074/jbc.M109.030130
  10. Hwang P, Wiloughby DS. Mechanisms behind pyrroloquino-line quinone supplementation on skeletal muscle mitochondrial biogenesis: possible synergistic effects with exercise.: Am Coll Nutr 2018;37:738-48. https://doi.org/10.1080/07315724.2018.1461146
  11. Mandala A, Dobrinskikh E, Janssen RC, et al. Maternal pyrroloquinoline quinone supplementation improves offspring liver bioactive lipid profiles throughout the lifespan and protects against the development of adult NAFLD. Int J Mol Sci 2022;23:6043. https://doi.org/10.3390/ijms23116043
  12. Ishak NSM, Ikemoto K, Kikuchi M, Ogawa M, Akutagawa K, Akagawa M. Pyrroloquin-oline quinone attenuates fat accumulation in obese mice fed with a high-fat diet, daphnia magna supplied with a high amount of food, and 3T3-L1 adipocytes. ACS Food Sci Technol 2021;1:1979-89. https://doi.org/10.1021/acsfoodscitech.1c00301
  13. Vanderfiyden BC, Telfer EE, Eppig JJ. Mouse oocytes promote proliferation of granulosa cells from preantral and antral follicles in vitro. Biol Reprod 1992;46:1196-204. https://doi.org/10.1095/biolreprod46.6.1196
  14. Wang CR, Yuan XW, Ji HW, Xu YN, Li YH, Kim NH. Chrysoeriol improves the early development potential of porcine oocytes by maintaining lipid homeostasis and improving mitochondrial function. Antioxidants 2024;13:122. https://doi.org/10.3390/antiox13010122
  15. Sovernigo TC, Adona PR, Monzani PS, et al. Effects of supplementation of medium with different antioxidants during in vitro maturation of bovine oocytes on subsequent embryo production. Reprod Domest Anim 2017;52:561-9. https://doi.org/10.1111/rda.12946
  16. Yin Z, Sun JT, Cui HD, et al. Tannin supplementation improves oocyte cytoplasmic matu-ration and subsequent embryo development in pigs. Antioxidants 2021;10:1594. https://doi.org/10.3390/antiox10101594
  17. Ferreira EM, Vireque AA, Adona PR, Meirelles FV, Ferriani RA, Navarro PAAS. Cyto-plasmic maturation of bovine oocytes: structural and biochemical modifications and acquisition of developmental competence. Theriogenology 2009;71:836-48. https://doi.org/10.1016/j.theriogenology.2008.10.023
  18. Duran HE, Simsek-Duran F, Oehninger SC, Jones HW Jr, Castora FJ. The association of reproductive senescence with mitochondrial quantity, function, and DNA integrity in human oocytes at different stages of maturation. Fertil Steril 2011;96:384-8. https://doi.org/10.1016/j.fertnstert.2011.05.
  19. Ge H, Tollner TL, Hu Z, et al. The importance of mitochondrial metabolic activity and mitochondrial DNA replication during oocyte maturation in vitro on oocyte quality and subsequent embryo developmental competence. Mol Reprod Dev 2012;79:392-401. https://doi.org/10.1002/mrd.22042
  20. Lee SK, Zhao MH, Kwon JW, et al. The association of mito-chondrial potential and copy number with pig oocyte maturation and developmental potential. J Reprod Dev 2014;60:128-35. https://doi.org/10.1262/jrd2013-098
  21. Zhao Z, Pu Y. Lixisenatide enhances mitochondrial biogenesis and function through regulating the CREB/PGC-1α pathway. Biochem Biophys Res Commun 2019;508:1120-5. https://doi.org/10.1016/j.bbrc.2018.11.135
  22. Jia L, Wang J, Cao H, Zhang X, Rong W, Xu Z. Activation of PGC-1α and mitochondrial biogenesis protects against prenatal hypoxicischemic brain injury. Neuroscience 2020;432:63-72. https://doi.org/10.1016/j.neuroscience.2020.02.035
  23. Niu YJ, Zhou W, Nie ZW, Shin KT, Cui XS. Melatonin enhances mitochondrial biogenesis and protects against rotenone-induced mitochondrial deficiency in early porcine embryos. J Pineal Res 2020;68:e12627. https://doi.org/10.1111/jpi.12627
  24. Nie J, Yan K, Sui L, et al. Mogroside V improves porcine oocyte in vitro maturation and subsequent embryonic development. Theriogenology 2020;141:35-40. https://doi.org/10.1016/j.theriogenology.2019.09.010
  25. He SY, Liu W, Huang CM, et al. Enhancing antioxidant levels and mitochondrial function in porcine oocyte maturation and embryonic development through notoginsenoside R1 supplementation. Reprod Domest Anim 2024;59:e14631. https://doi.org/10.1111/rda.14631
  26. Lee SH, Li XH, Lu QY, et al. Nobiletin enhances mitochondrial function by regulating SIRT1/PGC-1α signaling in porcine oocytes during in vitro maturation. Biochem Biophys Res Commun 2024;706:149747. https://doi.org/10.1016/j.bbrc.2024.149747
  27. Khazaei M, Aghaz F. Reactive oxygen species generation and use of antioxidants during in vitro maturation of oocytes. Int J Fertil Steril 2017;11:63-70. https://doi.org/10.22074/ijfs.2017.4995
  28. Wang L, Tang J, Wang L, et al. Oxidative stress in oocyte aging and female reproduction. J Cell Physiol 2021;236:7966-83. https://doi.org/10.1002/jcp.30468
  29. Wang F, Tian X, Zhang L, et al. Beneficial effect of resveratrol on bovine oocyte maturation and subsequent embryonic development after in vitro fertilization. Fertil Steril 2014;101:577-86.e1. https://doi.org/10.1016/j.fertnstert.2013.10.041
  30. Zhang H, Li C, Wen D, et al. Melatonin improves the quality of maternally aged oocytes by maintaining intercellular communication and antioxidant metabolite supply. Redox Biol 2022;49:102215. https://doi.org/10.1016/j.redox.2021.
  31. Jeong PS, Yang HJ, Jeon SB, et al. Luteolin supplementation during porcine oocyte maturation improves the developmental competence of parthenogenetic activation and cloned embryos. PeerJ 2023;11:e15618. https://doi.org/10.7717/peerj.
  32. Funahashi H, Cantley TC, Stumpf TT, Terlouw SL, Day BN. Use of low-salt culture medium for in vitro maturation of porcine oocytes is associated with elevated oocyte glutathione levels and enhanced male pronuclear formation after in vitro fertilization. Biol Reprod 1994;51:633-9. https://doi.org/10.1095/biolreprod51.4.633
  33. Zhou Z, Jia RX, Zhang G, et al. Using cysteine/cystine to overcome oxidative stress in goat oocytes and embryos cultured in vitro. Mol Med Rep 2016;14:1219-26. https://doi.org/10.3892/mmr.2016.5395
  34. Li J, Wang R, Chen Q, Tian Y, Gao L, Lei A. Salidroside improves porcine oocyte maturation and subsequent embryonic development by promoting lipid metabolism. Theriogenology 2022;192:89-96. https://doi.org/10.1016/j.theriogenology.2022.08.028
  35. Liu H, An ZY, Li ZY, et al. The ginsenoside Rh2 protects porcine oocytes against aging and oxidative stress by regulating SIRT1 expression and mitochondrial activity. Theriogenology 2023;200:125-35. https://doi.org/10.1016/j.theriogenology.2023.02.006
  36. Romek M, Gajda B, Krzysztofowicz E, Kepczynski M, Smorag Z. New technique to quantify the lipid composition of lipid droplets in porcine oocytes and pre-implantation embryos using Nile Red fluorescent probe. Theriogenology 2011;75:42-54. https://doi.org/10.1016/j.theriogenology.2010.06.040
  37. Dunning KR, Russell DL, Robker RL. Lipids and oocyte developmental competence: the role of fatty acids and β-oxidation. Reproduction 2014;148:R15-27. https://doi.org/10.1530/REP-13-0251
  38. Dunning KR, Cashman K, Russell DL, Thompson JG, Norman RJ, Robker RL. Beta-oxidation is essential for mouse oocyte developmental competence and early embryo development. Biol Reprod 2010;83:909-18. https://doi.org/10.1095/biolreprod.110.084145
  39. Paczkowski M, Silva E, Schoolcraft WB, Krisher RL. Comparative importance of fatty acid beta-oxidation to nuclear maturation, gene expression, and glucose metabolism in mouse, bovine, and porcine cumulus oocyte complexes. Biol Reprod 2013;88:111. https://doi.org/10.1095/biolreprod.113.108548
  40. Catandi GD, Cheng MH, Chicco AJ, Chen T, Carnevale EM. L-carnitine enhances de-velopmental potential of bovine oocytes matured under high lipid concentrations in vitro. Anim Reprod Sci 2023;252:107249. https://doi.org/10.1016/j.anireprosci.2023.107249