A behind-the-scenes role of BDNF in the survival and differentiation of spermatogonia.
Journal
Asian journal of andrology
ISSN: 1745-7262
Titre abrégé: Asian J Androl
Pays: China
ID NLM: 100942132
Informations de publication
Date de publication:
13 Aug 2024
13 Aug 2024
Historique:
received:
31
10
2023
accepted:
17
05
2024
medline:
23
8
2024
pubmed:
23
8
2024
entrez:
23
8
2024
Statut:
aheadofprint
Résumé
Mouse spermatogenesis entails the maintenance and self-renewal of spermatogonial stem cells (SSCs), which require a complex web-like signaling network transduced by various cytokines. Although brain-derived neurotrophic factor (BDNF) is expressed in Sertoli cells in the testis, and its receptor tropomyosin receptor kinase B (TrkB) is expressed in the spermatogonial population containing SSCs, potential functions of BDNF for spermatogenesis have not been uncovered. Here, we generate BDNF conditional knockout mice and find that BDNF is dispensable for in vivo spermatogenesis and fertility. However, in vitro, we reveal that BDNF-deficient germline stem cells (GSCs) exhibit growth potential not only in the absence of glial cell line-derived neurotrophic factor (GDNF), a master regulator for GSC proliferation, but also in the absence of other factors, including epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), and insulin. GSCs grown without these factors are prone to differentiation, yet they maintain expression of promyelocytic leukemia zinc finger (Plzf), an undifferentiated spermatogonial marker. Inhibition of phosphoinositide 3-kinase (PI3K), mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK), and Src pathways all interfere with the growth of BDNF-deficient GSCs. Thus, our findings suggest a role for BDNF in maintaining the undifferentiated state of spermatogonia, particularly in situations where there is a shortage of growth factors.
Identifiants
pubmed: 39177410
doi: 10.4103/aja202457
pii: 00129336-990000000-00225
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
Copyright © 2024 Copyright: ©The Author(s)(2024).
Références
Kanatsu-Shinohara M, Shinohara T. Spermatogonial stem cell self-renewal and development. Annu Rev Cell Dev Biol 2013;29:163–87.
Russell LD. Histological and Histopathological Evaluation of the Testis. Clearwater:Cache River Press;1990.
O'Donnell L, O'Bryan MK. Microtubules and spermatogenesis. Semin Cell Dev Biol 2014;30:45–54.
Kanatsu-Shinohara M, Ogonuki N, Inoue K, Miki H, Ogura A, et al. Long-term proliferation in culture and germline transmission of mouse male germline stem cells. Biol Reprod 2003;69:612–6.
Kanatsu-Shinohara M, Ogonuki N, Matoba S, Morimoto H, Ogura A, et al. Improved serum- and feeder-free culture of mouse germline stem cells. Biol Reprod 2014;91:88.
Kanatsu-Shinohara M, Inoue K, Ogonuki N, Morimoto H, Ogura A, et al. Serum- and feeder-free culture of mouse germline stem cells. Biol Reprod 2011;84:97–105.
Kanatsu-Shinohara M, Miki H, Inoue K, Ogonuki N, Toyokuni S, et al. Long-term culture of mouse male germline stem cells under serum-or feeder-free conditions. Biol Reprod 2005;72:985–91.
Kubota H, Avarbock MR, Brinster RL. Growth factors essential for self-renewal and expansion of mouse spermatogonial stem cells. Proc Natl Acad Sci U S A 2004;101:16489–94.
Sariola H, Saarma M. Novel functions and signalling pathways for GDNF. J Cell Sci 2003;116:3855–62.
Meng X, Lindahl M, Hyvönen ME, Parvinen M, de Rooij DG, et al. Regulation of cell fate decision of undifferentiated spermatogonia by GDNF. Science 2000;287:1489–93.
Kanatsu-Shinohara M. Genetic and epigenetic properties of mouse male germline stem cells during long-term culture. Development 2005;132:4155–63.
De Vita G, Melillo RM, Carlomagno F, Visconti R, Castellone MD, et al. Tyrosine 1062 of RET-MEN2A mediates activation of Akt (protein kinase B) and mitogen-activated protein kinase pathways leading to PC12 cell survival. Cancer Res 2000;60:3727–31.
Takahashi M. The GDNF/RET signaling pathway and human diseases. Cytokine Growth Factor Rev 2001;12:361–73.
Soppet D, Escandon E, Maragos J, Middlemas DS, Reid SW, et al. The neurotrophic factors brain-derived neurotrophic factor and neurotrophin-3 are ligands for the trkB tyrosine kinase receptor. Cell 1991;65:895–903.
Reichardt LF. Neurotrophin-regulated signalling pathways. Philos Trans R Soc Lond B Biol Sci 2006;361:1545–64.
Adachi N, Numakawa T, Richards M, Nakajima S, Kunugi H. New insight in expression, transport, and secretion of brain-derived neurotrophic factor:implications in brain-related diseases. World J Biol Chem 2014;5:409.
Park C, Choi WS, Kwon H, Kwon YK. Temporal and spatial expression of neurotrophins and their receptors during male germ cell development. Mol Cells 2001;12:360–7.
Müller D, Davidoff MS, Bargheer O, Paust HJ, Pusch W, et al. The expression of neurotrophins and their receptors in the prenatal and adult human testis:evidence for functions in Leydig cells. Histochem Cell Biol 2006;126:199–211.
Shirakawa T, Yaman-Deveci R, Tomizawa S, Kamizato Y, Nakajima K, et al. An epigenetic switch is crucial for spermatogonia to exit the undifferentiated state toward a kit-positive identity. Development 2013;140:3565–76.
Phillips BT, Gassei K, Orwig KE. Spermatogonial stem cell regulation and spermatogenesis. Philos Trans R Soc Lond B Biol Sci 2010;365:1663–78.
Hermann BP, Sukhwani M, Hansel MC, Orwig KE. Spermatogonial stem cells in higher primates:are there differences from those in rodents?. Reproduction 2010;139:479–93.
Hermann BP, Sukhwani M, Simorangkir DR, Chu T, Plant TM, et al. Molecular dissection of the male germ cell lineage identifies putative spermatogonial stem cells in rhesus macaques. Hum Reprod 2009;24:1704–16.
MacLean JA, Hu Z, Welborn JP, Song HW, Rao MK, et al. The RHOX homeodomain proteins regulate the expression of insulin and other metabolic regulators in the testis. J Biol Chem 2013;288:34809–25.
LaFever L, Drummond-Barbosa D. Direct control of germline stem cell division and cyst growth by neural insulin in Drosophila. Science 2005;309:1071–3.
McLeod CJ, Wang L, Wong C, Jones DL. Stem cell dynamics in response to nutrient availability. Curr Biol 2010;20:2100–5.
Lee J, Kanatsu-Shinohara M, Inoue K, Ogonuki N, Miki H, et al. Akt mediates self-renewal division of mouse spermatogonial stem cells. Development 2007;134:1853–9.
Hasegawa K, Namekawa SH, Saga Y. MEK/ERK signaling directly and indirectly contributes to the cyclical self-renewal of spermatogonial stem cells. Stem Cells 2013;31:2517–27.
Lee J, Kanatsu-Shinohara M, Morimoto H, Kazuki Y, Takashima S, et al. Genetic reconstruction of mouse spermatogonial stem cell self-renewal in vitro by ras-cyclin D2 activation. Cell Stem Cell 2009;5:76–86.
Puri P, Phillips BT, Suzuki H, Orwig KE, Rajkovic A, et al. The transition from stem cell to progenitor spermatogonia and male fertility requires the SHP2 protein tyrosine phosphatase. Stem Cells 2014;32:741–53.
He Z, Jiang J, Kokkinaki M, Golestaneh N, Hofmann MC, et al. Gdnf upregulates c-Fos transcription via the Ras/Erk1/2 pathway to promote mouse spermatogonial stem cell proliferation. Stem Cells 2008;26:266–78.
Ishii K, Kanatsu-Shinohara M, Toyokuni S, Shinohara T. FGF2 mediates mouse spermatogonial stem cell self-renewal via upregulation of Etv5 and Bcl6b through MAP2K1 activation. Development 2012;139:1734–43.
Lucas BE, Fields C, Joshi N, Hofmann MC. Mono-(2-ethylhexyl)-phthalate (MEHP) affects ERK-dependent GDNF signalling in mouse stem-progenitor spermatogonia. Toxicology 2012;299:10–9.
Oatley JM, Avarbock MR, Brinster RL. Glial cell line-derived neurotrophic factor regulation of genes essential for self-renewal of mouse spermatogonial stem cells is dependent on src family kinase signaling. J Biol Chem 2007;282:25842–51.
Sharma M, Braun RE. Cyclical expression of GDNF is required for spermatogonial stem cell homeostasis. Development 2018;145:dev151555.
Takashima S, Kanatsu-Shinohara M, Tanaka T, Morimoto H, Inoue K, et al. Functional differences between GDNF-dependent and FGF2-dependent mouse spermatogonial stem cell self-renewal. Stem Cell Reports 2015;4:1–14.
Sharma HS. Post-Traumatic Application of Brain-Derived Neurotrophic Factor and Glia-Derived Neurotrophic Factor on the Rat Spinal Cord Enhances Neuroprotection and Improves Motor Function. Vienna:Springer;2006 329–34.
Zurn AD, Winkel L, Menoud A, Djabali K, Aebischer P. Combined effects of GDNF, BDNF, and CNTF on motoneuron differentiation in vitro. J Neurosci Res 1996;44:133–41.
Ferrini F, Salio C, Boggio EM, Merighi A. Interplay of BDNF and GDNF in the mature spinal somatosensory system and its potential therapeutic relevance. Curr Neuropharmacol 2021;19:1225–45.
Giehl KM, Schütte A, Mestres P, Yan Q. The survival-promoting effect of glial cell line-derived neurotrophic factor on axotomized corticospinal neurons in vivo is mediated by an endogenous brain-derived neurotrophic factor mechanism. J Neurosci 1998;18:7351–60.
Morikawa M, Derynck R, Miyazono K. TGF-βand the TGF-βfamily:context-dependent roles in cell and tissue physiology. Cold Spring Harb Perspect Biol 2016;8:a021873.
Kopan R, Ilagan MX. The canonical Notch signaling pathway:unfolding the activation mechanism. Cell 2009;137:216–33.