小鼠精子发生需要精原干细胞（SSC）的维持和自我更新，这需要由各种细胞因子转导的复杂的网状信号网络。尽管脑源性神经营养因子（BDNF）在睾丸的支持细胞中表达，其受体原肌球蛋白受体激酶B（TrkB）在含有SSC的精原细胞群中表达，但BDNF对精子发生的潜在功能尚未被发现。在这里，我们培育了 BDNF 条件性敲除小鼠，发现 BDNF 对于体内精子发生和生育能力是不可或缺的。然而，在体外，我们发现BDNF缺陷的生殖干细胞（GSC）不仅在缺乏胶质细胞源性神经营养因子（GDNF）（GSC增殖的主要调节因子）的情况下表现出生长潜力，而且在缺乏其他因素，包括表皮生长因子（EGF）、碱性成纤维细胞生长因子（bFGF）和胰岛素。在没有这些因子的情况下生长的 GSC 易于分化，但它们仍保持早幼粒细胞白血病锌指 (Plzf)（一种未分化精原细胞标记）的表达。磷酸肌醇 3 激酶 (PI3K)、丝裂原激活蛋白激酶 (MAPK)/细胞外信号调节激酶 (ERK) 和 Src 通路的抑制都会干扰 BDNF 缺陷的 GSC 的生长。因此，我们的研究结果表明 BDNF 在维持精原细胞的未分化状态中发挥着作用，特别是在生长因子短缺的情况下。版权所有 © 2024 版权所有：©作者(2024)。

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.Copyright © 2024 Copyright: ©The Author(s)(2024).