Volume 45 Issue 1
Jan.  2024
Turn off MathJax
Article Contents
Yi Li, Xuehui Li, Ding Ye, Ru Zhang, Chengjie Liu, Mudan He, Houpeng Wang, Wei Hu, Yonghua Sun. Endogenous biosynthesis of docosahexaenoic acid (DHA) regulates fish oocyte maturation by promoting pregnenolone production. Zoological Research, 2024, 45(1): 176-188. doi: 10.24272/j.issn.2095-8137.2023.032
Citation: Yi Li, Xuehui Li, Ding Ye, Ru Zhang, Chengjie Liu, Mudan He, Houpeng Wang, Wei Hu, Yonghua Sun. Endogenous biosynthesis of docosahexaenoic acid (DHA) regulates fish oocyte maturation by promoting pregnenolone production. Zoological Research, 2024, 45(1): 176-188. doi: 10.24272/j.issn.2095-8137.2023.032

Endogenous biosynthesis of docosahexaenoic acid (DHA) regulates fish oocyte maturation by promoting pregnenolone production

doi: 10.24272/j.issn.2095-8137.2023.032
Supplementary data to this article can be found online.
The authors declare that they have no competing interests.
Y.H.S. conceived and designed the study and supervised the analyses. Y.L., X.H.L., D.Y., R.Z., and C.J.L. prepared the data. Y.L. and Y.H.S. analyzed the data. Y.L., M.D.H., and H.P.W. prepared the draft of the manuscript. W.H. provided resources. Y.L. and Y.H.S. revised and finalized the manuscript. All authors read and approved the final version of the manuscript.
Funds:  This study was supported by the Strategic Priority Research Program of the Chinese Academy of Sciences (Precision Seed Design and Breeding, XDA24010108), National Natural Science Foundation of China (31972780 & 31721005), National Key R&D Program of China (2018YFA0801000), and State Key Laboratory of Freshwater Ecology and Biotechnology (2019FBZ05)
More Information
  • Corresponding author: E-mail: yhsun@ihb.ac.cn
  • Received Date: 2023-03-15
  • Accepted Date: 2023-04-04
  • Published Online: 2023-09-09
  • Publish Date: 2024-01-18
  • Omega-3 polyunsaturated fatty acids (n-3 PUFAs), particularly docosahexaenoic acid (22:6n-3, DHA), play crucial roles in the reproductive health of vertebrates, including humans. Nevertheless, the underlying mechanism related to this phenomenon remains largely unknown. In this study, we employed two zebrafish genetic models, i.e., elovl2-/- mutant as an endogenous DHA-deficient model and fat1 (omega-3 desaturase encoding gene) transgenic zebrafish as an endogenous DHA-rich model, to investigate the effects of DHA on oocyte maturation and quality. Results show that the elovl2-/- mutants had much lower fecundity and poorer oocyte quality than the wild-type controls, while the fat1 zebrafish had higher fecundity and better oocyte quality than wild-type controls. DHA deficiency in elovl2-/- embryos led to defects in egg activation, poor microtubule stability, and reduced pregnenolone levels. Further study revealed that DHA promoted pregnenolone synthesis by enhancing transcription of cyp11a1, which encodes the cholesterol side-chain cleavage enzyme, thereby stabilizing microtubule assembly during oogenesis. In turn, the hypothalamic-pituitary-gonadal axis was enhanced by DHA. In conclusion, using two unique genetic models, our findings demonstrate that endogenously synthesized DHA promotes oocyte maturation and quality by promoting pregnenolone production via transcriptional regulation of cyp11a1.
  • Supplementary data to this article can be found online.
    The authors declare that they have no competing interests.
    Y.H.S. conceived and designed the study and supervised the analyses. Y.L., X.H.L., D.Y., R.Z., and C.J.L. prepared the data. Y.L. and Y.H.S. analyzed the data. Y.L., M.D.H., and H.P.W. prepared the draft of the manuscript. W.H. provided resources. Y.L. and Y.H.S. revised and finalized the manuscript. All authors read and approved the final version of the manuscript.
  • loading
  • [1]
    Agarwal A, Aponte-Mellado A, Premkumar BJ, et al. 2012. The effects of oxidative stress on female reproduction: a review. Reproductive Biology and Endocrinology, 10: 49. doi: 10.1186/1477-7827-10-49
    [2]
    Akhmanova A, Steinmetz MO. 2015. Control of microtubule organization and dynamics: two ends in the limelight. Nature Reviews Molecular Cell Biology, 16(12): 711−726. doi: 10.1038/nrm4084
    [3]
    Arita M, Bianchini F, Aliberti J, et al. 2005. Stereochemical assignment, antiinflammatory properties, and receptor for the omega-3 lipid mediator resolvin E1. Journal of Experimental Medicine, 201(5): 713−722. doi: 10.1084/jem.20042031
    [4]
    Arita M, Ohira T, Sun YP, et al. 2007. Resolvin E1 selectively interacts with leukotriene B4 receptor BLT1 and ChemR23 to regulate inflammation. The Journal of Immunology, 178(6): 3912−3917. doi: 10.4049/jimmunol.178.6.3912
    [5]
    Cerri RLA, Juchem SO, Chebel RC, et al. 2009. Effect of fat source differing in fatty acid profile on metabolic parameters, fertilization, and embryo quality in high-producing dairy cows. Journal of Dairy Science, 92(4): 1520−1531. doi: 10.3168/jds.2008-1614
    [6]
    Chiu YH, Karmon AE, Gaskins AJ, et al. 2018. Serum omega-3 fatty acids and treatment outcomes among women undergoing assisted reproduction. Human Reproduction, 33(1): 156−165. doi: 10.1093/humrep/dex335
    [7]
    Gu L, Liu HL, Gu X, et al. 2015. Metabolic control of oocyte development: linking maternal nutrition and reproductive outcomes. Cellular and Molecular Life Sciences, 72(2): 251−271. doi: 10.1007/s00018-014-1739-4
    [8]
    Han LR, Yu J, Chen YY, et al. 2018. Immunomodulatory activity of docosahexenoic acid on RAW264.7 cells activation through GPR120-mediated signaling pathway. Journal of Agricultural and Food Chemistry, 66(4): 926−934. doi: 10.1021/acs.jafc.7b05894
    [9]
    He MD, Jiao SB, Zhang R, et al. 2022. Translational control by maternal Nanog promotes oogenesis and early embryonic development. Development, 149(24): dev201213. doi: 10.1242/dev.201213
    [10]
    He MD, Zhang R, Jiao SB, et al. 2020. Nanog safeguards early embryogenesis against global activation of maternal β-catenin activity by interfering with TCF factors. PLoS Biology, 18(7): e3000561. doi: 10.1371/journal.pbio.3000561
    [11]
    Hilgendorf KI, Johnson CT, Mezger A, et al. 2019. Omega-3 fatty acids activate ciliary FFAR4 to control adipogenesis. Cell, 179(6): 1289−1305.e21. doi: 10.1016/j.cell.2019.11.005
    [12]
    Hirasawa A, Tsumaya K, Awaji T, et al. 2005. Free fatty acids regulate gut incretin glucagon-like peptide-1 secretion through GPR120. Nature Medicine, 11(1): 90−94. doi: 10.1038/nm1168
    [13]
    Hoo JY, Kumari Y, Shaikh MF, et al. 2016. Zebrafish: a versatile animal model for fertility research. BioMed Research International, 2016: 9732780.
    [14]
    Hsu HJ, Hsu NC, Hu MC, et al. 2006a. Steroidogenesis in zebrafish and mouse models. Molecular and Cellular Endocrinology, 248(1-2): 160−163. doi: 10.1016/j.mce.2005.10.011
    [15]
    Hsu HJ, Liang MR, Chen CT, et al. 2006b. Pregnenolone stabilizes microtubules and promotes zebrafish embryonic cell movement. Nature, 439(7075): 480−483. doi: 10.1038/nature04436
    [16]
    Hsu HJ, Lin JC, Chung BC. 2009. Zebrafish cyp11a1 and hsd3b genes: structure, expression and steroidogenic development during embryogenesis. Molecular and Cellular Endocrinology, 312(1-2): 31−34. doi: 10.1016/j.mce.2009.07.030
    [17]
    Hu MC, Hsu HJ, Guo IC, et al. 2004. Function of Cyp11a1 in animal models. Molecular and Cellular Endocrinology, 215(1-2): 95−100. doi: 10.1016/j.mce.2003.11.024
    [18]
    Janati Idrissi S, Slezec-Frick V, Le Bourhis D, et al. 2022. Effect of DHA on the quality of in vitro produced bovine embryos. Theriogenology, 187: 102−111. doi: 10.1016/j.theriogenology.2022.04.026
    [19]
    Jesuthasan S, Strähle U. 1997. Dynamic microtubules and specification of the zebrafish embryonic axis. Current Biology, 7(1): 31−42. doi: 10.1016/S0960-9822(06)00025-X
    [20]
    Jiao SB, He MD, Sun YH. 2023. Research progress and several key scientific questions in studies of fish egg quality. Acta Hydrobiologica Sinica, 47(6): 1007−1024. (in Chinese)
    [21]
    Katakura M, Hashimoto M, Shahdat HM, et al. 2009. Docosahexaenoic acid promotes neuronal differentiation by regulating basic helix-loop-helix transcription factors and cell cycle in neural stem cells. Neuroscience, 160(3): 651−660. doi: 10.1016/j.neuroscience.2009.02.057
    [22]
    Kniazeva M, Sieber M, McCauley S, et al. 2003. Suppression of the ELO-2 FA elongation activity results in alterations of the fatty acid composition and multiple physiological defects, including abnormal ultradian rhythms, in Caenorhabditis elegans. Genetics, 163(1): 159–169.
    [23]
    Krisher RL. 2013. In vivo and in vitro environmental effects on mammalian oocyte quality. Annual Review of Animal Biosciences, 1: 393−417. doi: 10.1146/annurev-animal-031412-103647
    [24]
    Lauritzen L, Brambilla P, Mazzocchi A, et al. 2016. DHA effects in brain development and function. Nutrients, 8(1): 6. doi: 10.3390/nu8010006
    [25]
    Li YY, Chen WZ, Sun ZW, et al. 2004. Effects of n-3 HUFA content in broodstock diets on reproductive performance and seasonal changes of plasma sex steroids levels in Plectorhynchus cinctus. Zoological Research, 25(3): 249–255. (in Chinese)
    [26]
    Liu CJ, Ye D, Wang HP, et al. 2020. Elovl2 but not Elovl5 is essential for the biosynthesis of docosahexaenoic acid (DHA) in zebrafish: Insight from a comparative gene knockout study. Marine Biotechnology, 22(5): 613−619. doi: 10.1007/s10126-020-09992-1
    [27]
    Loehfelm A, Elder MK, Boucsein A, et al. 2020. Docosahexaenoic acid prevents palmitate induced insulin dependent impairments of neuronal health. The FASEB Journal, 34(3): 4635−4652. doi: 10.1096/fj.201902517R
    [28]
    Lu FI, Sun YH, Wei CY, et al. 2014. Tissue specific derepression of TCF/LEF controls the activity of the Wnt/β-catenin pathway. Nature Communications, 5: 5368. doi: 10.1038/ncomms6368
    [29]
    MacRae CA, Peterson RT. 2015. Zebrafish as tools for drug discovery. Nature Reviews Drug Discovery, 14(10): 721−731. doi: 10.1038/nrd4627
    [30]
    Maillard V, Desmarchais A, Durcin M, et al. 2018. Docosahexaenoic acid (DHA) effects on proliferation and steroidogenesis of bovine granulosa cells. Reproductive Biology and Endocrinology, 16(1): 40. doi: 10.1186/s12958-018-0357-7
    [31]
    Masoudi R, Sharafi M, Zare Shahneh A, et al. 2016. Effect of dietary fish oil supplementation on ram semen freeze ability and fertility using soybean lecithin-and egg yolk-based extenders. Theriogenology, 86(6): 1583−1588. doi: 10.1016/j.theriogenology.2016.05.018
    [32]
    Miao YL, Cui Z, Gao Q, et al. 2020. Nicotinamide mononucleotide supplementation reverses the declining quality of maternally aged oocytes. Cell Reports 32(5): 107987.
    [33]
    Monroig O, Tocher DR, Castro LFC. 2018. Polyunsaturated fatty acid biosynthesis and metabolism in fish. In: Burdge GC. Polyunsaturated Fatty Acid Metabolism. Amsterdam: Elsevier, 31–60.
    [34]
    Muskiet FAJ, Fokkema MR, Schaafsma A, et al. 2004. Is Docosahexaenoic Acid (DHA) Essential? Lessons from DHA status regulation, our ancient diet, epidemiology and randomized controlled trials. The Journal of Nutrition, 134(1): 183−186. doi: 10.1093/jn/134.1.183
    [35]
    Nehra D, Le HD, Fallon EM, et al. 2012. Prolonging the female reproductive lifespan and improving egg quality with dietary omega-3 fatty acids. Aging Cell, 11(6): 1046−1054. doi: 10.1111/acel.12006
    [36]
    Oh DY, Talukdar S, Bae EJ, et al. 2010. GPR120 is an omega-3 fatty acid receptor mediating potent anti-inflammatory and insulin-sensitizing effects. Cell, 142(5): 687−698. doi: 10.1016/j.cell.2010.07.041
    [37]
    Ojeda SR, Naor Z, Negro-Vilar A. 1979. The role of prostaglandins in the control of gonadotropin and prolactin secretion. Prostaglandins and Medicine, 2(4): 249−275. doi: 10.1016/0161-4630(79)90060-0
    [38]
    Olsen SF, Halldorsson TI, Li M, et al. 2019. Examining the effect of fish oil supplementation in Chinese pregnant women on gestation duration and risk of preterm delivery. The Journal of Nutrition, 149(11): 1942−1951. doi: 10.1093/jn/nxz153
    [39]
    Pang SC, Wang HP, Li KY, et al. 2014. Double transgenesis of humanized fat1 and fat2 genes promotes omega-3 polyunsaturated fatty acids synthesis in a zebrafish model. Marine Biotechnology, 16(5): 580−593. doi: 10.1007/s10126-014-9577-9
    [40]
    Pusceddu MM, Nolan YM, Green HF, et al. 2016. The omega-3 polyunsaturated fatty acid docosahexaenoic acid (DHA) reverses corticosterone-induced changes in cortical neurons. International Journal of Neuropsychopharmacology, 19(6): pyv130.
    [41]
    Qi XL, Shang MY, Chen C, et al. 2019. Dietary supplementation with linseed oil improves semen quality, reproductive hormone, gene and protein expression related to testosterone synthesis in aging layer breeder roosters. Theriogenology, 131: 9−15. doi: 10.1016/j.theriogenology.2019.03.016
    [42]
    Serrano-García N, Fernández-Valverde F, Luis-Garcia ER, et al. 2018. Docosahexaenoic acid protection in a rotenone induced Parkinson's model: prevention of tubulin and synaptophysin loss, but no association with mitochondrial function. Neurochemistry International, 121: 26−37. doi: 10.1016/j.neuint.2018.10.015
    [43]
    Shin JI, Jeon YJ, Lee S, et al. 2019. G-protein-coupled receptor 120 mediates DHA-induced apoptosis by regulating IP3R, ROS and, ER stress levels in cisplatin-resistant cancer cells. Molecules and Cells, 42(3): 252−261.
    [44]
    Stoffel W, Holz B, Jenke B, et al. 2008. Δ6-desaturase (FADS2) deficiency unveils the role of ω3- and ω6-polyunsaturated fatty acids. The EMBO Journal, 27(17): 2281−2292. doi: 10.1038/emboj.2008.156
    [45]
    Sun QY, Lai LX, Park KW, et al. 2001. Dynamic events are differently mediated by microfilaments, microtubules, and mitogen-activated protein kinase during porcine oocyte maturation and fertilization in vitro. Biology of Reproduction, 64(3): 879−889. doi: 10.1095/biolreprod64.3.879
    [46]
    Swanson D, Block R, Mousa SA. 2012. Omega-3 fatty acids EPA and DHA: health benefits throughout life. Advances in Nutrition, 3(1): 1−7. doi: 10.3945/an.111.000893
    [47]
    Tocher DR. 2003. Metabolism and functions of lipids and fatty acids in teleost fish. Reviews in Fisheries Science, 11(2): 107−184. doi: 10.1080/713610925
    [48]
    Tran DQ, Ramos EH, Belsham DD. 2016. Induction of Gnrh mRNA expression by the ω-3 polyunsaturated fatty acid docosahexaenoic acid and the saturated fatty acid palmitate in a GnRH-synthesizing neuronal cell model, mHypoA-GnRH/GFP. Molecular and Cellular Endocrinology, 426: 125−135. doi: 10.1016/j.mce.2016.02.019
    [49]
    Tran LD, Hino H, Quach H, et al. 2012. Dynamic microtubules at the vegetal cortex predict the embryonic axis in zebrafish. Development, 139(19): 3644−3652. doi: 10.1242/dev.082362
    [50]
    Vrablik TL, Watts JL. 2013. Polyunsaturated fatty acid derived signaling in reproduction and development: insights from Caenorhabditis elegans and Drosophila melanogaster. Molecular Reproduction & Development, 80(4): 244–259.
    [51]
    Wang YQ, Ye D, Zhang FH, et al. 2022. Cyp11a2 Is essential for oocyte development and spermatogonial stem cell differentiation in zebrafish. Endocrinology, 163(2): bqab258. doi: 10.1210/endocr/bqab258
    [52]
    Wang X, Zhu J, Wang H, et al. 2023. Induced formation of primordial germ cells from zebrafish blastomeres by germplasm factors. Nature Communications, 14(1): 7918. doi: 10.1038/s41467-023-43587-3
    [53]
    Wathes DC, Abayasekara DRE, Aitken RJ. 2007. Polyunsaturated fatty acids in male and female reproduction. Biology of Reproduction, 77(2): 190−201. doi: 10.1095/biolreprod.107.060558
    [54]
    Wei CY, Wang HP, Zhu ZY, et al. 2014. Transcriptional factors Smad1 and Smad9 act redundantly to mediate zebrafish ventral specification downstream of Smad5. Journal of Biological Chemistry, 289(10): 6604−6618. doi: 10.1074/jbc.M114.549758
    [55]
    Weng JH, Liang MR, Chen CH, et al. 2013. Pregnenolone activates CLIP-170 to promote microtubule growth and cell migration. Nature Chemical Biology, 9(10): 636−642. doi: 10.1038/nchembio.1321
    [56]
    Wonnacott KE, Kwong WY, Hughes J, et al. 2010. Dietary omega-3 and -6 polyunsaturated fatty acids affect the composition and development of sheep granulosa cells, oocytes and embryos. Reproduction, 139(1): 57−69. doi: 10.1530/REP-09-0219
    [57]
    Xu HG, Cao L, Wei YL, et al. 2017. Effects of different dietary DHA: EPA ratios on gonadal steroidogenesis in the marine teleost, tongue sole (Cynoglossus semilaevis). British Journal of Nutrition, 118(3): 179−188. doi: 10.1017/S0007114517001891
    [58]
    Xu SS, Li Y, Wang HP, et al. 2023. Depletion of stearoyl-CoA desaturase (scd) leads to fatty liver disease and defective mating behavior in zebrafish. Zoological Research, 44(1): 63−77. doi: 10.24272/j.issn.2095-8137.2022.167
    [59]
    Yang YJ, Wang Y, Li Z, et al. 2017. Sequential, divergent, and cooperative requirements of Foxl2a and Foxl2b in ovary development and maintenance of zebrafish. Genetics, 205(4): 1551−1572. doi: 10.1534/genetics.116.199133
    [60]
    Ye D, Tu YX, Wang HP, et al. 2022. A landscape of differentiated biological processes involved in the initiation of sex differentiation in zebrafish. Water Biology and Security, 1(3): 100059. doi: 10.1016/j.watbs.2022.100059
    [61]
    Ye D, Zhu L, Zhang QF, et al. 2019. Abundance of early embryonic primordial germ cells promotes zebrafish female differentiation as revealed by lifetime labeling of germline. Marine Biotechnology, 21(2): 217−228. doi: 10.1007/s10126-019-09874-1
    [62]
    Zadravec D, Tvrdik P, Guillou H, et al. 2011. ELOVL2 controls the level of n-6 28: 5 and 30: 5 fatty acids in testis, a prerequisite for male fertility and sperm maturation in mice. Journal of Lipid Research, 52(2): 245−255. doi: 10.1194/jlr.M011346
    [63]
    Zeituni EM, Farber SA. 2016. Studying lipid metabolism and transport during zebrafish development. In: Kawakami K, Patton E, Orger M. Zebrafish: Methods and Protocols. New York: Humana Press, 237–255.
    [64]
    Zhang QF, Ye D, Wang HP, et al. 2020. Zebrafish cyp11c1 knockout reveals the roles of 11-ketotestosterone and Cortisol in sexual development and reproduction. Endocrinology, 161(6): bqaa048. doi: 10.1210/endocr/bqaa048
    [65]
    Zhang R, Tu YX, Ye D, et al. 2022. A germline-specific regulator of mitochondrial fusion is required for maintenance and differentiation of germline stem and progenitor cells. Advanced Science, 9(36): 2203631. doi: 10.1002/advs.202203631
    [66]
    Zhang TT, Xu J, Wang YM, et al. 2019a. Health benefits of dietary marine DHA/EPA-enriched glycerophospholipids. Progress in Lipid Research, 75: 100997. doi: 10.1016/j.plipres.2019.100997
    [67]
    Zhang XF, Pang SC, Liu CJ, et al. 2019b. A novel dietary source of EPA and DHA: metabolic engineering of an important freshwater species-common carp by fat1-transgenesis. Marine Biotechnology, 21(2): 171−185. doi: 10.1007/s10126-018-9868-7
    [68]
    Zhou Q. 2013. Advances in the study of neuroendocrinological regulation of kisspeptin in fish reproduction. Zoological Research, 34(5): 519−530.
    [69]
    Zhu YH, Tan QS, Zhang LS, et al. 2019. The migration of docosahexenoic acid (DHA) to the developing ovary of female zebrafish (Danio rerio). Comparative Biochemistry and Physiology Part A:Molecular & Integrative Physiology, 233: 97−105.
  • ZR-2023-032-Supplementary Materials.zip
  • 加载中

Catalog

    通讯作者: 陈斌, bchen63@163.com
    • 1. 

      沈阳化工大学材料科学与工程学院 沈阳 110142

    1. 本站搜索
    2. 百度学术搜索
    3. 万方数据库搜索
    4. CNKI搜索

    Figures(6)

    Article Metrics

    Article views (832) PDF downloads(162) Cited by()
    Proportional views
    Related

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return