Abstract
The present study aimed to investigate whether the Gfra1/Gdnf and/or Kit/Kitlg regulatory pathways could be involved in the regulation of spermatogonial cell proliferation and/or differentiation in fish. Homologs of the mammalian gfra1, gdnf, kitr, and kitlg genes were identified in gnathostomes and reliable orthologous relationships were established using phylogenetic reconstructions and analyses of syntenic chromosomal fragments. Gene duplications and losses occurred specifically in teleost fish and members of the Salmoninae family including rainbow trout (Oncorhynchus mykiss) and Atlantic salmon (Salmo salar). Some duplicated genes exhibited distinct spatiotemporal expression profiles and were differently regulated by hormones in rainbow trout. Undifferentiated type A spermatogonia expressed higher levels of kitrb and kitra2 making them possible target cells for the gonadal kitlgb and somatic kitlga before the onset of spermatogenesis. Interestingly, gdnfa and gdnfb ohnologous genes were poorly expressed before the onset of spermatogenesis. The expression level of gdnfb was correlated with that of the vasa gene suggesting that the late increased abundance of gdnfb during spermatogenesis onset was due to the increased number of spermatogonial cells. gfra1a2 was expressed in undifferentiated type A spermatogonia whereas gfra1a1 was mainly detected in somatic cells. These observations indicate that the germinal gdnfb ligand could exert autocrine and paracrine functions on spermatogonia and on testicular somatic cells, respectively. Fsh and androgens inhibited gfra1a2 and gdnfb whereas gfra1a1 was stimulated by Fsh, androgens, and 17α, 20β progesterone. Finally, our data provide evidences that the molecular identity of the male germ stem cells changes during ontogenesis prior to spermatogenesis onset.
Similar content being viewed by others
References
Amores A, Force A, Yan YL, Joly L, Amemiya C, Fritz A, Ho RK, Langeland J, Prince V, Wang YL, Westerfield M, Ekker M, Postlethwait JH (1998) Zebrafish hox clusters and vertebrate genome evolution. Science 282:1711–1714
Bellaiche J, Goupil AS, Sambroni E, Lareyre JJ, Le Gac F (2014a) Gdnf-gfra1 pathway is expressed in a spermatogenetic-dependent manner and is regulated by fsh in a fish testis. Biol Reprod 91:94
Bellaiche J, Lareyre JJ, Cauty C, Yano A, Allemand I, Le Gac F (2014b) Spermatogonial stem cell quest: nanos2, marker of a subpopulation of undifferentiated a spermatogonia in trout testis. Biol Reprod 90:79
Berthelot C, Brunet F, Chalopin D, Juanchich A, Bernard M, Noel B, Bento P, Da Silva C, Labadie K, Alberti A, Aury JM, Louis A, Dehais P, Bardou P, Montfort J, Klopp C, Cabau C, Gaspin C, Thorgaard GH, Boussaha M, Quillet E, Guyomard R, Galiana D, Bobe J, Volff JN, Genet C, Wincker P, Jaillon O, Roest Crollius H, Guiguen Y (2014) The rainbow trout genome provides novel insights into evolution after whole-genome duplication in vertebrates. Nat Commun 5:3657
Bosseboeuf A, Gautier A, Auvray P, Mazan S, Sourdaine P (2013) Characterization of spermatogonial markers in the mature testis of the dogfish (Scyliorhinus canicula L.). Reproduction 147:125–139
Braydich-Stolle L, Nolan C, Dym M, Hofmann MC (2005) Role of glial cell line-derived neurotrophic factor in germ-line stem cell fate. Ann N Y Acad Sci 1061:94–99
Brunet FG, Roest Crollius H, Paris M, Aury JM, Gibert P, Jaillon O, Laudet V, Robinson-Rechavi M (2006) Gene loss and evolutionary rates following whole-genome duplication in teleost fishes. Mol Biol Evol 23:1808–1816
Busada JT, Kaye EP, Renegar RH, Geyer CB (2014) Retinoic acid induces multiple hallmarks of the prospermatogonia-to-spermatogonia transition in the neonatal mouse. Biol Reprod 90:64
De Felici M (2000) Regulation of primordial germ cell development in the mouse. Int J Dev Biol 44:575–580
Dolci S, Williams DE, Ernst MK, Resnick JL, Brannan CI, Lock LF, Lyman SD, Boswell HS, Donovan PJ (1991) Requirement for mast cell growth factor for primordial germ cell survival in culture. Nature 352:809–811
Fan L, Moon J, Wong TT, Crodian J, Collodi P (2008) Zebrafish primordial germ cell cultures derived from vasa::RFP transgenic embryos. Stem Cells Dev 17:585–597
Gautier A, Bosseboeuf A, Auvray P, Sourdaine P (2014) Maintenance of potential spermatogonial stem cells in vitro by GDNF treatment in a chondrichthyan model (Scyliorhinus canicula L.). Biol Reprod 91:91
Hara K, Nakagawa T, Enomoto H, Suzuki M, Yamamoto M, Simons BD, Yoshida S (2014) Mouse spermatogenic stem cells continually interconvert between equipotent singly isolated and syncytial states. Cell Stem Cell 14:658–672
He Z, Jiang J, Kokkinaki M, Golestaneh N, Hofmann MC, Dym M (2008) Gdnf upregulates c-Fos transcription via the Ras/Erk1/2 pathway to promote mouse spermatogonial stem cell proliferation. Stem Cells 26:266–278
Helsel AR, Yang QE, Oatley MJ, Lord T, Sablitzky F, Oatley JM (2017) ID4 levels dictate the stem cell state in mouse spermatogonia. Development 144:624–634
Jing S, Wen D, Yu Y, Holst PL, Luo Y, Fang M, Tamir R, Antonio L, Hu Z, Cupples R, Louis JC, Hu S, Altrock BW, Fox GM (1996) GDNF-induced activation of the ret protein tyrosine kinase is mediated by GDNFR-alpha, a novel receptor for GDNF. Cell 85:1113–1124
Kanatsu-Shinohara M, Inoue K, Takashima S, Takehashi M, Ogonuki N, Morimoto H, Nagasawa T, Ogura A, Shinohara T (2012) Reconstitution of mouse spermatogonial stem cell niches in culture. Cell Stem Cell 11:567–578
Kumar S, Stecher G, Tamura K (2016) MEGA7: molecular evolutionary genetics analysis version 7.0 for bigger datasets. Mol Biol Evol 33:1870–1874
Lacerda SM, Batlouni SR, Costa GM, Segatelli TM, Quirino BR, Queiroz BM, Kalapothakis E, Franca LR (2010) A new and fast technique to generate offspring after germ cells transplantation in adult fish: the Nile tilapia (Oreochromis niloticus) model. PLoS One 5:e10740
Lacerda SM, Costa GM, da Silva MA, Campos-Junior PH, Segatelli TM, Peixoto MT, Resende RR, de Franca LR (2013) Phenotypic characterization and in vitro propagation and transplantation of the Nile tilapia (Oreochromis niloticus) spermatogonial stem cells. Gen Comp Endocrinol 192:95–106
Lien S, Koop BF, Sandve SR, Miller JR, Kent MP, Nome T, Hvidsten TR, Leong JS, Minkley DR, Zimin A, Grammes F, Grove H, Gjuvsland A, Walenz B, Hermansen RA, von Schalburg K, Rondeau EB, Di Genova A, Samy JK, Olav Vik J, Vigeland MD, Caler L, Grimholt U, Jentoft S, Vage DI, de Jong P, Moen T, Baranski M, Palti Y, Smith DR, Yorke JA, Nederbragt AJ, Tooming-Klunderud A, Jakobsen KS, Jiang X, Fan D, Hu Y, Liberles DA, Vidal R, Iturra P, Jones SJ, Jonassen I, Maass A, Omholt SW, Davidson WS (2016) The Atlantic salmon genome provides insights into rediploidization. Nature 533:200–205
Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C (T)) method. Methods 25:402–408
Loir M (1999) Spermatogonia of rainbow trout: I. Morphological characterization, mitotic activity, and survival in primary cultures of testicular cells. Mol Reprod Dev 53:422–433
Loir M, Sourdaine P (1994) Testes cells: isolation and culture. In: Hochachka PW, Mommsen TP (eds) Biochemistry and molecular biology of fishes: analytical techniques. Elsevier, Amsterdam, pp 249–272
Meng X, Lindahl M, Hyvonen ME, Parvinen M, de Rooij DG, Hess MW, Raatikainen-Ahokas A, Sainio K, Rauvala H, Lakso M, Pichel JG, Westphal H, Saarma M, Sariola H (2000) Regulation of cell fate decision of undifferentiated spermatogonia by GDNF. Science 287:1489–1493
Meyer A, Van de Peer Y (2005) From 2R to 3R: evidence for a fish-specific genome duplication (FSGD). Bioessays 27:937–945
Nakagawa T, Sharma M, Nabeshima Y, Braun RE, Yoshida S (2010) Functional hierarchy and reversibility within the murine spermatogenic stem cell compartment. Science 328:62–67
Nakajima S, Hayashi M, Kouguchi T, Yamaguchi K, Miwa M, Yoshizaki G (2014) Expression patterns of gdnf and gfralpha1 in rainbow trout testis. Gene Expr Patterns 14:111–120
Naughton CK, Jain S, Strickland AM, Gupta A, Milbrandt J (2006) Glial cell-line derived neurotrophic factor-mediated RET signaling regulates spermatogonial stem cell fate. Biol Reprod 74:314–321
Nobrega RH, Greebe CD, van de Kant H, Bogerd J, de Franca LR, Schulz RW (2010) Spermatogonial stem cell niche and spermatogonial stem cell transplantation in zebrafish. PLoS One 5:e12808
Ohno S (1970) Evolution by gene duplication. Springer-Verlag, Berlin, p 160
Okutsu T, Suzuki K, Takeuchi Y, Takeuchi T, Yoshizaki G (2006) Testicular germ cells can colonize sexually undifferentiated embryonic gonad and produce functional eggs in fish. Proc Natl Acad Sci U S A 103:2725–2729
Orth JM, Jester WF Jr (1995) NCAM mediates adhesion between gonocytes and Sertoli cells in cocultures from testes of neonatal rats. J Androl 16:389–399
Panda RP, Barman HK, Mohapatra C (2011) Isolation of enriched carp spermatogonial stem cells from Labeo rohita testis for in vitro propagation. Theriogenology 76:241–251
Pesce M, Di Carlo A, De Felici M (1997) The c-kit receptor is involved in the adhesion of mouse primordial germ cells to somatic cells in culture. Mech Dev 68:37–44
Pitetti JL, Calvel P, Zimmermann C, Conne B, Papaioannou MD, Aubry F, Cederroth CR, Urner F, Fumel B, Crausaz M, Docquier M, Herrera PL, Pralong F, Germond M, Guillou F, Jegou B, Nef S (2013) An essential role for insulin and IGF1 receptors in regulating sertoli cell proliferation, testis size, and FSH action in mice. Mol Endocrinol 27:814–827
Rolland AD, Lareyre JJ, Goupil AS, Montfort J, Ricordel MJ, Esquerre D, Hugot K, Houlgatte R, Chalmel F, Le Gac F (2009) Expression profiling of rainbow trout testis development identifies evolutionary conserved genes involved in spermatogenesis. BMC Genomics 10:546
Runyan C, Schaible K, Molyneaux K, Wang Z, Levin L, Wylie C (2006) Steel factor controls midline cell death of primordial germ cells and is essential for their normal proliferation and migration. Development 133:4861–4869
Sambroni E, Rolland AD, Lareyre JJ, Le GF (2013) FSH and LH have common and distinct effects on gene expression in rainbow trout testis. J Mol Endocrinol 50:1–18
Schulz RW, Menting S, Bogerd J, Franca LR, Vilela DA, Godinho HP (2005) Sertoli cell proliferation in the adult testis--evidence from two fish species belonging to different orders. Biol Reprod 73:891–898
Tadokoro Y, Yomogida K, Ohta H, Tohda A, Nishimune Y (2002) Homeostatic regulation of germinal stem cell proliferation by the GDNF/FSH pathway. Mech Dev 113:29–39
Thompson JD, Higgins DG, Gibson TJ (1994) CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Res 22:4673–4680
Treanor JJ, Goodman L, de Sauvage F, Stone DM, Poulsen KT, Beck CD, Gray C, Armanini MP, Pollock RA, Hefti F, Phillips HS, Goddard A, Moore MW, Buj-Bello A, Davies AM, Asai N, Takahashi M, Vandlen R, Henderson CE, Rosenthal A (1996) Characterization of a multicomponent receptor for GDNF. Nature 382:80–83
Western PS, Miles DC, van den Bergen JA, Burton M, Sinclair AH (2008) Dynamic regulation of mitotic arrest in fetal male germ cells. Stem Cells 26:339–347
Yang Y, Han C (2010) GDNF stimulates the proliferation of cultured mouse immature Sertoli cells via its receptor subunit NCAM and ERK1/2 signaling pathway. BMC Cell Biol 11:78
Acknowledgements
The authors thank the animal care facility of the LPGP research department, especially Frédéric Borel, Amélie Patinote, and Cécile Melin. The authors thank Laurent Labbé and Lionel Goardon from the INRA PEIMA experimental fish farm for providing the monosex males and Drs. Alexis Fostier and Yann Guiguen for the gift of the rainbow trout YY sperm.
Funding
The research leading to these results has received funding from the European Community’s Horizon 2020 research infrastructure project (INFRAIA-1-2014/2015) under grant agreement no. 652831 (project AQUAEXCEL2020) and from the French National Research Agency under grand agreement no. 11-INBS-0003 (CRB anim project). Ahmed Maouche gratefully acknowledges the Britany province (Région Bretagne) and the INRA PHASE department for the funding received towards his PhD.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Maouche, A., Curran, E., Goupil, AS. et al. New insights into the evolution, hormonal regulation, and spatiotemporal expression profiles of genes involved in the Gfra1/Gdnf and Kit/Kitlg regulatory pathways in rainbow trout testis. Fish Physiol Biochem 44, 1599–1616 (2018). https://doi.org/10.1007/s10695-018-0547-4
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10695-018-0547-4