A behind-the-scenes role of BDNF in the survival and differentiation of spermatogonia
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 trop...
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| Format: | Article |
| Language: | English |
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Wolters Kluwer Medknow Publications
2025-01-01
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| Series: | Asian Journal of Andrology |
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| Online Access: | https://journals.lww.com/10.4103/aja202457 |
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| author | Shin-ichi Tomizawa Kazushige Kuroha Michio Ono Kuniko Nakajima Kazuyuki Ohbo |
| author_facet | Shin-ichi Tomizawa Kazushige Kuroha Michio Ono Kuniko Nakajima Kazuyuki Ohbo |
| author_sort | Shin-ichi Tomizawa |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-ce4f4284a8184162b250e24fc4220f82 |
| institution | DOAJ |
| issn | 1008-682X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Wolters Kluwer Medknow Publications |
| record_format | Article |
| series | Asian Journal of Andrology |
| spelling | doaj-art-ce4f4284a8184162b250e24fc4220f822025-08-20T03:15:47ZengWolters Kluwer Medknow PublicationsAsian Journal of Andrology1008-682X2025-01-01271374310.4103/aja202457A behind-the-scenes role of BDNF in the survival and differentiation of spermatogoniaShin-ichi TomizawaKazushige KurohaMichio OnoKuniko NakajimaKazuyuki OhboMouse 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.https://journals.lww.com/10.4103/aja202457bdnfspermatogenesisspermatogoniastem cells |
| spellingShingle | Shin-ichi Tomizawa Kazushige Kuroha Michio Ono Kuniko Nakajima Kazuyuki Ohbo A behind-the-scenes role of BDNF in the survival and differentiation of spermatogonia Asian Journal of Andrology bdnf spermatogenesis spermatogonia stem cells |
| title | A behind-the-scenes role of BDNF in the survival and differentiation of spermatogonia |
| title_full | A behind-the-scenes role of BDNF in the survival and differentiation of spermatogonia |
| title_fullStr | A behind-the-scenes role of BDNF in the survival and differentiation of spermatogonia |
| title_full_unstemmed | A behind-the-scenes role of BDNF in the survival and differentiation of spermatogonia |
| title_short | A behind-the-scenes role of BDNF in the survival and differentiation of spermatogonia |
| title_sort | behind the scenes role of bdnf in the survival and differentiation of spermatogonia |
| topic | bdnf spermatogenesis spermatogonia stem cells |
| url | https://journals.lww.com/10.4103/aja202457 |
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