The Regulation of Spermatogonial Stem Cells in an Adult Testis by Glial Cell Line-Derived Neurotrophic Factor.

The Regulation of Spermatogonial Stem Cells in an Adult Testis by Glial Cell Line-Derived Neurotrophic Factor.
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DOI:
10.3389/fendo.2022.896390
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发表时间:
2022
影响因子:
5.2
通讯作者:
Wright, William W.
Wright, William W.
中科院分区:
医学2区
文献类型:
--
作者:
Wright, William W.

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本文综述了胶质细胞源性神经营养因子(GDNF)对成年睾丸精原干细胞(SSCs)的体内调控作用。为了研究成年小鼠睾丸,我们通过化学遗传学方法可逆地抑制GDNF对SSCs的刺激。这种抑制减少了复制并增加了SSC的分化,并且9天的抑制使可移植SSC数量减少了90%。随着更持续的抑制,所有的SSC都丢失了,睾丸最终类似于只有支持细胞(SCO)综合征的人类睾丸。这种相似性促使我们去问GDNF的表达是否在这些不育的人类睾丸中异常低。是的FGF2和FGF8的表达也减少,但一些SCO睾丸含有SSC。为了评估由于GDNF信号传导不足而耗尽的SSC池的可能重建,我们抑制然后恢复对小鼠SSC的信号传导。部分重建发生,这表明GDNF作为治疗男性SCO综合征。
This review focuses on the in vivo regulation of spermatogonial stem cells (SSCs) in adult testes by glial cell line-derived neurotrophic factor (GDNF). To study adult mouse testes, we reversibly inhibited GDNF stimulation of SSCs via a chemical-genetic approach. This inhibition diminishes replication and increases differentiation of SSCs, and inhibition for 9 days reduces transplantable SSC numbers by 90%. With more sustained inhibition, all SSCs are lost, and testes eventually resemble human testes with Sertoli cell-only (SCO) syndrome. This resemblance prompted us to ask if GDNF expression is abnormally low in these infertile human testes. It is. Expression of FGF2 and FGF8 is also reduced, but some SCO testes contain SSCs. To evaluate the possible rebuilding of an SSC pool depleted due to inadequate GDNF signaling, we inhibited and then restored signaling to mouse SSCs. Partial rebuilding occurred, suggesting GDNF as therapy for men with SCO syndrome.
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