Leptin modulates oocyte maturation by a central and a direct pathway in zebrafish

in Journal of Endocrinology
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  • 1 Institute of Zoology, University of Cologne, Cologne, Germany

Correspondence should be addressed to M Michel: maximichel@gmail.com
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Loss of LEPR function (LOF) in mammals leads to diverse phenotypes including morbid obesity and infertility while zebrafish show relatively minor phenotypes. This however allows the study of LEPR LOF in the absence of the detrimental effects of hyperglycemia or obesity. Here, we show evidence that leptin plays a role in the central as well as peripheral regulation of the hypothalamic–pituitary–gonadal (HPG) axis in zebrafish. Animals with a Lepr LOF show dysregulated pituitary HPG genes as well as evidence that oocytes mature slower and/or exhibit an increased rate of atresia. In culture, Lepr LOF attenuates the effect of 17α-20β-dihydroxy-4 pregnen-3-one in promoting germinal vesicle breakdown (GVBD) and increases the rate of GVBD as well as attenuates the rate of oocyte atresia.

 

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  • Ahi EP, Brunel M, Tsakoumis E & Schmitz M 2019 Transcriptional study of appetite regulating genes in the brain of zebrafish (Danio rerio) with impaired leptin signalling. Scientific Reports 9 20166. (https://doi.org/10.1038/s41598-019-56779-z)

    • Search Google Scholar
    • Export Citation
  • Almog B, Gold R, Tajima K, Dantes A, Salim K, Rubinstein M, Barkan D, Homburg R, Lessing JB & Nevo N et al.2001 Leptin attenuates follicular apoptosis and accelerates the onset of puberty in immature rats. Molecular and Cellular Endocrinology 183 179191. (https://doi.org/10.1016/s0303-7207(0100543-3)

    • Search Google Scholar
    • Export Citation
  • Audira G, Sarasamma S, Chen JR, Juniardi S, Sampurna BP, Liang ST, Lai YH, Lin GM, Hsieh MC & Hsiao CD 2018 Zebrafish mutants carrying leptin a (lepa) gene deficiency display obesity, anxiety, less aggression and fear, and circadian rhythm and color preference dysregulation. International Journal of Molecular Sciences 19 4038. (https://doi.org/10.3390/ijms19124038)

    • Search Google Scholar
    • Export Citation
  • Bagivalu Lakshminarasimha A, Page-McCaw P, Mockel D, Gremse F & Michel M 2021 Leptin system loss of function in the absence of obesity in zebrafish. Journal of Endocrinology 251 4152. (https://doi.org/10.1530/JOE-21-0037)

    • Search Google Scholar
    • Export Citation
  • Brand M, Granato M & Nüsslein-Volhard C 2002 Keeping and raising zebrafish. In Zebrafish: A Practical Approach, pp. 737. Eds Nüsslein-Volhard C, Dahm R. Oxford: UK: Oxford University Press. (ISBN: 9780199638086)

    • Search Google Scholar
    • Export Citation
  • Bretschneider LH & De Wit J 1947 Sexual Endocrinology of Non-Mammalian Vertebrates. New York: Elsevier Publishing. (https://catalog.hathitrust.org/Record/001503566)

    • Search Google Scholar
    • Export Citation
  • Chen J, Cao M, Zhang A, Shi M, Tao B, Li Y, Wang Y, Zhu Z, Trudeau VL & Hu W 2018 Growth hormone overexpression disrupts reproductive status through actions on leptin. Frontiers in Endocrinology 9 131. (https://doi.org/10.3389/fendo.2018.00131)

    • Search Google Scholar
    • Export Citation
  • Chisada S, Kurokawa T, Murashita K, Ronnestad I, Taniguchi Y, Toyoda A, Sakaki Y, Takeda S & Yoshiura Y 2014 Leptin receptor-deficient (knockout) medaka, Oryzias latipes, show chronical up-regulated levels of orexigenic neuropeptides, elevated food intake and stage specific effects on growth and fat allocation. General and Comparative Endocrinology 195 920. (https://doi.org/10.1016/j.ygcen.2013.10.008)

    • Search Google Scholar
    • Export Citation
  • Chou SH & Mantzoros C 2014 20 years of leptin: role of leptin in human reproductive disorders. Journal of Endocrinology 223 T49T62. (https://doi.org/10.1530/JOE-14-0245)

    • Search Google Scholar
    • Export Citation
  • Cone RD 2006 Studies on the physiological functions of the melanocortin system. Endocrine Reviews 27 736749. (https://doi.org/10.1210/er.2006-0034)

    • Search Google Scholar
    • Export Citation
  • Deck CA, Honeycutt JL, Cheung E, Reynolds HM & Borski RJ 2017 Assessing the functional role of leptin in energy homeostasis and the stress response in vertebrates. Frontiers in Endocrinology 8 63. (https://doi.org/10.3389/fendo.2017.00063)

    • Search Google Scholar
    • Export Citation
  • Denver RJ, Bonett RM & Boorse GC 2011 Evolution of leptin structure and function. Neuroendocrinology 94 2138. (https://doi.org/10.1159/000328435)

    • Search Google Scholar
    • Export Citation
  • Dupuis L, Schuermann Y, Cohen T, Siddappa D, Kalaiselvanraja A, Pansera M, Bordignon V & Duggavathi R 2014 Role of leptin receptors in granulosa cells during ovulation. Reproduction 147 221229. (https://doi.org/10.1530/REP-13-0356)

    • Search Google Scholar
    • Export Citation
  • Engin AB 2017 What is lipotoxicity? Advances in Experimental Medicine and Biology 960 197220. (https://doi.org/10.1007/978-3-319-48382-5_8)

    • Search Google Scholar
    • Export Citation
  • Fei F, Sun SY, Yao YX & Wang X 2017 Generation and phenotype analysis of zebrafish mutations of obesity-related genes lepr and mc4r. Sheng Li Xue Bao 69 6169. (https: //doi.org/10.13294/j.aps.2016.0076)

    • Search Google Scholar
    • Export Citation
  • Gong N & Bjornsson BT 2014 Leptin signaling in the rainbow trout central nervous system is modulated by a truncated leptin receptor isoform. Endocrinology 155 24452455. (https://doi.org/10.1210/en.2013-2131)

    • Search Google Scholar
    • Export Citation
  • Gong Y, Luo Z, Zhu QL, Zheng JL, Tan XY, Chen QL, Lin YC & Lu RH 2013 Characterization and tissue distribution of leptin, leptin receptor and leptin receptor overlapping transcript genes in yellow catfish Pelteobagrus fulvidraco. General and Comparative Endocrinology 182 16. (https://doi.org/10.1016/j.ygcen.2012.11.006)

    • Search Google Scholar
    • Export Citation
  • Gonzalez-Kother P, Oliva ME, Tanguy A & Moraga D 2020 A review of the potential genes implicated in follicular atresia in teleost fish. Marine Genomics 50 100704. (https://doi.org/10.1016/j.margen.2019.100704)

    • Search Google Scholar
    • Export Citation
  • Hamm ML, Bhat GK, Thompson WE & Mann DR 2004 Folliculogenesis is impaired and granulosa cell apoptosis is increased in leptin-deficient mice. Biology of Reproduction 71 6672. (https://doi.org/10.1095/biolreprod.104.027292)

    • Search Google Scholar
    • Export Citation
  • He J, Ding Y, Nowik N, Jager C, Eeza MNH, Alia A, Baelde HJ & Spaink HP 2021 Leptin deficiency affects glucose homeostasis and results in adiposity in zebrafish. Journal of Endocrinology 249 125134. (https://doi.org/10.1530/JOE-20-0437)

    • Search Google Scholar
    • Export Citation
  • Kamstra K, Rizwan MZ, Grattan DR, Horsfield JA & Tups A 2022 Leptin regulates glucose homeostasis via the canonical Wnt pathway in the zebrafish. FASEB Journal 36 e22207. (https://doi.org/10.1096/fj.202101764R)

    • Search Google Scholar
    • Export Citation
  • Kang J, Hu J, Karra R, Dickson AL, Tornini VA, Nachtrab G, Gemberling M, Goldman JA, Black BL & Poss KD 2016 Modulation of tissue repair by regeneration enhancer elements. Nature 532 201206. (https://doi.org/10.1038/nature17644)

    • Search Google Scholar
    • Export Citation
  • Karlsson C, Lindell K, Svensson E, Bergh C, Lind P, Billig H, Carlsson LM & Carlsson B 1997 Expression of functional leptin receptors in the human ovary. Journal of Clinical Endocrinology and Metabolism 82 41444148. (https://doi.org/10.1210/jcem.82.12.4446)

    • Search Google Scholar
    • Export Citation
  • Kurokawa T & Murashita K 2009 Genomic characterization of multiple leptin genes and a leptin receptor gene in the Japanese medaka, Oryzias latipes. General and Comparative Endocrinology 161 229237. (https://doi.org/10.1016/j.ygcen.2009.01.008)

    • Search Google Scholar
    • Export Citation
  • LaFave MC, Varshney GK, Vemulapalli M, Mullikin JC & Burgess SM 2014 A defined zebrafish line for high-throughput genetics and genomics: NHGRI-1. Genetics 198 167170. (https://doi.org/10.1534/genetics.114.166769)

    • Search Google Scholar
    • Export Citation
  • Levavi-Sivan B, Bogerd J, Mananos EL, Gomez A & Lareyre JJ 2010 Perspectives on fish gonadotropins and their receptors. General and Comparative Endocrinology 165 412437. (https://doi.org/10.1016/j.ygcen.2009.07.019)

    • Search Google Scholar
    • Export Citation
  • Li J & Ge W 2020 Zebrafish as a model for studying ovarian development: recent advances from targeted gene knockout studies. Molecular and Cellular Endocrinology 507 110778. (https://doi.org/10.1016/j.mce.2020.110778)

    • Search Google Scholar
    • Export Citation
  • Liu Q, Chen Y, Copeland D, Ball H, Duff RJ, Rockich B & Londraville RL 2010 Expression of leptin receptor gene in developing and adult zebrafish. General and Comparative Endocrinology 166 346355. (https://doi.org/10.1016/j.ygcen.2009.11.015)

    • Search Google Scholar
    • Export Citation
  • Liu Q, Dalman M, Chen Y, Akhter M, Brahmandam S, Patel Y, Lowe J, Thakkar M, Gregory AV & Phelps D et al.2012 Knockdown of leptin A expression dramatically alters zebrafish development. General and Comparative Endocrinology 178 562572. (https://doi.org/10.1016/j.ygcen.2012.07.011)

    • Search Google Scholar
    • Export Citation
  • Löhr H, Hess S, Pereira MMA, Reinoss P, Leibold S, Schenkel C, Wunderlich CM, Kloppenburg P, Bruning JC & Hammerschmidt M 2018 Diet-induced growth is regulated via acquired leptin resistance and engages a Pomc-somatostatin-growth hormone circuit. Cell Reports 23 17281741. (https://doi.org/10.1016/j.celrep.2018.04.018)

    • Search Google Scholar
    • Export Citation
  • Marvel M, Spicer OS, Wong TT, Zmora N & Zohar Y 2018 Knockout of the Gnrh genes in zebrafish: effects on reproduction and potential compensation by reproductive and feeding-related neuropeptides. Biology of Reproduction 99 565577. (https://doi.org/10.1093/biolre/ioy078)

    • Search Google Scholar
    • Export Citation
  • Marvel MM, Spicer OS, Wong TT, Zmora N & Zohar Y 2019 Knockout of Gnrh2 in zebrafish (Danio rerio) reveals its roles in regulating feeding behavior and oocyte quality. General and Comparative Endocrinology 280 1523. (https://doi.org/10.1016/j.ygcen.2019.04.002)

    • Search Google Scholar
    • Export Citation
  • Marvel M, Levavi-Sivan B, Wong TT, Zmora N & Zohar Y 2021 Gnrh2 maintains reproduction in fasting zebrafish through dynamic neuronal projection changes and regulation of gonadotropin synthesis, oogenesis, and reproductive behaviors. Scientific Reports 11 6657. (https://doi.org/10.1038/s41598-021-86018-3)

    • Search Google Scholar
    • Export Citation
  • McCurley AT & & Callard GV 2008 Characterization of housekeeping genes in zebrafish: male-female differences and effects of tissue type, developmental stage and chemical treatment. BMC Mol Biol 9 102.(https://doi.org/10.1186/1471-2199-9-102)

    • Search Google Scholar
    • Export Citation
  • Michel M, Page-McCaw PS, Chen W & Cone RD 2016 Leptin signaling regulates glucose homeostasis, but not adipostasis, in the zebrafish. PNAS 113 30843089. (https://doi.org/10.1073/pnas.1513212113)

    • Search Google Scholar
    • Export Citation
  • Molina AM, Abril N, Morales-Prieto N, Monterde JG, Lora AJ, Ayala N & Moyano R 2018 Evaluation of toxicological endpoints in female zebrafish after bisphenol A exposure. Food and Chemical Toxicology 112 1925. (https://doi.org/10.1016/j.fct.2017.12.026)

    • Search Google Scholar
    • Export Citation
  • Ohga H, Matsumori K, Kodama R, Kitano H, Nagano N, Yamaguchi A & Matsuyama M 2015 Two leptin genes and a leptin receptor gene of female chub mackerel (Scomber japonicus): molecular cloning, tissue distribution and expression in different obesity indices and pubertal stages. General and Comparative Endocrinology 222 8898. (https://doi.org/10.1016/j.ygcen.2015.06.002)

    • Search Google Scholar
    • Export Citation
  • Pang Y & Thomas P 2009 Involvement of estradiol-17beta and its membrane receptor, G protein coupled receptor 30 (GPR30) in regulation of oocyte maturation in zebrafish, Danio rario. General and Comparative Endocrinology 161 5861. (https://doi.org/10.1016/j.ygcen.2008.10.003)

    • Search Google Scholar
    • Export Citation
  • Paolucci M, Coccia E, Imperatore R & Varricchio E 2020 A cross-talk between leptin and 17beta-estradiol in vitellogenin synthesis in rainbow trout Oncorhynchus mykiss liver. Fish Physiology and Biochemistry 46 331344. (https://doi.org/10.1007/s10695-019-00720-8)

    • Search Google Scholar
    • Export Citation
  • Peyon P, Zanuy S & Carrillo M 2001 Action of leptin on in vitro luteinizing hormone release in the European sea bass (Dicentrarchus labrax). Biology of Reproduction 65 15731578. (https://doi.org/10.1095/biolreprod65.5.1573)

    • Search Google Scholar
    • Export Citation
  • Prokop JW, Duff RJ, Ball HC, Copeland DL & Londraville RL 2012 Leptin and leptin receptor: analysis of a structure to function relationship in interaction and evolution from humans to fish. Peptides 38 326336. (https://doi.org/10.1016/j.peptides.2012.10.002)

    • Search Google Scholar
    • Export Citation
  • Qian B, Xue L & Huang H 2016 Liver transcriptome analysis of the large yellow croaker (Larimichthys crocea) during fasting by using RNA-Seq. PLoS ONE 11 e0150240. (https://doi.org/10.1371/journal.pone.0150240)

    • Search Google Scholar
    • Export Citation
  • Ronnestad I, Gomes AS, Murashita K, Angotzi R, Jonsson E & Volkoff H 2017 Appetite-controlling endocrine systems in teleosts. Frontiers in Endocrinology 8 73. (https://doi.org/10.3389/fendo.2017.00073)

    • Search Google Scholar
    • Export Citation
  • Ruiz-Cortes ZT, Martel-Kennes Y, Gevry NY, Downey BR, Palin MF & Murphy BD 2003 Biphasic effects of leptin in porcine granulosa cells. Biology of Reproduction 68 789796. (https://doi.org/10.1095/biolreprod.102.010702)

    • Search Google Scholar
    • Export Citation
  • Ryan NK, Van der Hoek KH, Robertson SA & Norman RJ 2003 Leptin and leptin receptor expression in the rat ovary. Endocrinology 144 50065013. (https://doi.org/10.1210/en.2003-0584)

    • Search Google Scholar
    • Export Citation
  • Seki S, Kouya T, Tsuchiya R, Valdez Jr DM, Jin B, Hara T, Saida N, Kasai M & Edashige K 2008 Development of a reliable in vitro maturation system for zebrafish oocytes. Reproduction 135 285292. (https://doi.org/10.1530/REP-07-0416)

    • Search Google Scholar
    • Export Citation
  • Selman K, Wallace RA, Sarka A & Qi X 1993 Stages of oocyte development in the zebrafish, Brachydanio rerio. Journal of Morphology 218 203224. (https://doi.org/10.1002/jmor.1052180209)

    • Search Google Scholar
    • Export Citation
  • Selman K, Petrino TR & Wallace RA 1994 Experimental conditions for oocyte maturation in the zebrafish, Brachydanio-rerio. Journal of Experimental Zoology 269 538550. (https://doi.org/10.1002/jez.1402690607)

    • Search Google Scholar
    • Export Citation
  • Serke H, Nowicki M, Kosacka J, Schroder T, Kloting N, Bluher M, Kallendrusch S & Spanel-Borowski K 2012 Leptin-deficient (ob/ob) mouse ovaries show fatty degeneration, enhanced apoptosis and decreased expression of steroidogenic acute regulatory enzyme. International Journal of Obesity 36 10471053. (https://doi.org/10.1038/ijo.2011.220)

    • Search Google Scholar
    • Export Citation
  • Shang G, Peng X, Ji C, Zhai G, Ruan Y, Lou Q, Jin X, He J, Wang H & Yin Z 2019 Steroidogenic acute regulatory protein and luteinizing hormone are required for normal ovarian steroidogenesis and oocyte maturation in zebrafishdagger. Biology of Reproduction 101 760770. (https://doi.org/10.1093/biolre/ioz132)

    • Search Google Scholar
    • Export Citation
  • Sheffer-Babila S, Sun Y, Israel DD, Liu SM, Neal-Perry G & Chua Jr SC 2013 Agouti-related peptide plays a critical role in leptin’s effects on female puberty and reproduction. American Journal of Physiology: Endocrinology and Metabolism 305 E1512E1520. (https://doi.org/10.1152/ajpendo.00241.2013)

    • Search Google Scholar
    • Export Citation
  • Song YF, Tan XY, Pan YX, Zhang LH & Chen QL 2018 Fatty acid beta-oxidation is essential in leptin-mediated oocytes maturation of yellow catfish Pelteobagrus fulvidraco. International Journal of Molecular Sciences 19 1457. (https://doi.org/10.3390/ijms19051457)

    • Search Google Scholar
    • Export Citation
  • Spicer LJ & Francisco CC 1997 The adipose obese gene product, leptin: evidence of a direct inhibitory role in ovarian function. Endocrinology 138 33743379. (https://doi.org/10.1210/endo.138.8.5311)

    • Search Google Scholar
    • Export Citation
  • Spicer OS, Wong TT, Zmora N & Zohar Y 2016 Targeted mutagenesis of the hypophysiotropic Gnrh3 in zebrafish (Danio rerio) reveals no effects on reproductive performance. PLoS ONE 11 e0158141. (https://doi.org/10.1371/journal.pone.0158141)

    • Search Google Scholar
    • Export Citation
  • Tang Y, Yu J, Li H, Xu P, Li J & Ren H 2013 Molecular cloning, characterization and expression analysis of multiple leptin genes in Jian carp (Cyprinus carpio var. Jian). Comparative Biochemistry and Physiology: Part B, Biochemistry and Molecular Biology 166 133140. (https://doi.org/10.1016/j.cbpb.2013.07.009)

    • Search Google Scholar
    • Export Citation
  • Tian J, He G, Mai K & Liu C 2015 Effects of postprandial starvation on mRNA expression of endocrine-, amino acid and peptide transporter-, and metabolic enzyme-related genes in zebrafish (Danio rerio). Fish Physiology and Biochemistry 41 773787. (https://doi.org/10.1007/s10695-015-0045-x)

    • Search Google Scholar
    • Export Citation
  • Trudeau VL 2018 Facing the challenges of neuropeptide gene knockouts: why do they not inhibit reproduction in adult teleost fish? Frontiers in Neuroscience 12 302. (https://doi.org/10.3389/fnins.2018.00302)

    • Search Google Scholar
    • Export Citation
  • Tsakoumis E, Ahi EP & Schmitz M 2022 Impaired leptin signaling causes subfertility in female zebrafish. Molecular and Cellular Endocrinology 546 111595. (https://doi.org/10.1016/j.mce.2022.111595)

    • Search Google Scholar
    • Export Citation
  • Weil C, Le Bail PY, Sabin N & Le Gac F 2003 In vitro action of leptin on FSH and LH production in rainbow trout (Onchorynchus mykiss) at different stages of the sexual cycle. General and Comparative Endocrinology 130 212. (https://doi.org/10.1016/s0016-6480(0200504-x)

    • Search Google Scholar
    • Export Citation
  • Welch EL, Eno CC, Nair S, Lindeman RE & Pelegri F 2017 Functional manipulation of maternal gene products using in vitro oocyte maturation in zebrafish. Journal of Visualized Experiments 138 55213. (https://doi.org/10.3791/55213)

    • Search Google Scholar
    • Export Citation
  • Witthames PR, Armstrong M, Thorsen A, Solemdal P & Kjesbu OS 2013 Contrasting development and delivery of realised fecundity in Atlantic cod (Gadus morhua) stocks from cold and warm waters. Fisheries Research 138 128138. (https://doi.org/10.1016/j.fishres.2012.08.016)

    • Search Google Scholar
    • Export Citation
  • Zhao H, Zeng C, Yi S, Wan S, Chen B & Gao Z 2015 Leptin genes in blunt snout bream: cloning, phylogeny and expression correlated to gonads development. International Journal of Molecular Sciences 16 2760927624. (https://doi.org/10.3390/ijms161126044)

    • Search Google Scholar
    • Export Citation