Endogenous EGF maintains Sertoli germ cell anchoring junction integrity and is required for early recovery from acute testicular ischemia/reperfusion injury.
Endogenous EGF maintains Sertoli germ cell anchoring junction integrity and is required for early recovery from acute testicular ischemia/reperfusion injury.
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DOI：
10.1530/rep-12-0336
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发表时间：
2013-02
期刊：
影响因子：
3.8
通讯作者：
Shun Zhang;Yixiong Zeng;J. Qu;Ya-ning Luo;Xiaohong Wang;Wei Li
中科院分区：
文献类型：
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作者：
Shun Zhang;Yixiong Zeng;J. Qu;Ya-ning Luo;Xiaohong Wang;Wei Li
外源性表皮生长因子（EGF）可改善急性缺血再灌注（IR）应激后睾丸损伤，但其分子基础尚不清楚。本文研究了内源性EGF在睾丸恢复中的作用以及所涉及的潜在细胞内信号通路。小鼠睾丸IR损伤可显著提高再灌注初期内源性Egf的表达水平。再灌注后3 h， EGF受体Egfr （ErbB1）的表达相应上调。涎腺切除术剥夺大部分循环EGF加重了睾丸损害（特别是粗质精母细胞），增强了生殖细胞凋亡，随后导致IR损伤后减数分裂分化受损。从机制上讲，内源性EGF信号对于睾丸早期恢复过程中支持生殖细胞锚定连接动力学的适当维持似乎是不可或缺的。我们还在一个成熟的大鼠Sertoli生殖细胞共培养模型中提供了体外证据，表明内源性EGF对生殖细胞在睾丸IR损伤后的促存活作用至少部分是通过磷脂酰肌醇3-激酶/pAkt途径介导的。总之，我们的研究结果表明，在睾丸恢复早期，内源性EGF的增加可能在内分泌级联上起作用，协调支持细胞和生殖细胞之间的密切相互作用，并可能作为睾丸IR应激反应中不可或缺的防御机制。该领域未来的研究将进一步阐明这一复杂的发病机制。
Administration of exogenous epidermal growth factor (EGF) improves testicular injury after acute ischemia-reperfusion (IR) stress, but the molecular basis is poorly understood. The role of endogenous EGF in testicular recovery and the underlying intracellular signaling pathways involved were herein investigated. In mice, testicular IR injury significantly enhanced the expression level of endogenous Egf at the very beginning of reperfusion. Expression of EGF receptor (Egfr (ErbB1)) was accordingly upregulated 3 h after reperfusion. Deprivation of majority of circulated EGF by sialoadenectomy aggravated testicular detriment (especially in pachytene spermatocytes), enhanced germ cell apoptosis, and thereafter resulted in impaired meiotic differentiation after IR insult. Mechanistically, endogenous EGF signaling appeared to be indispensable for the proper maintenance of Sertoli germ cells anchoring junction dynamics during the early testicular recovery. We also provided the in vitro evidences in a well-established rat Sertoli germ cell co-cultures model that the pro-survival effect of endogenous EGF on germ cells in response to testicular IR insult is mediated, at least in part, via the phosphatidylinositol 3-kinase/pAkt pathway. Collectively, our results suggest that the augment of endogenous EGF during the early testicular recovery may act on top of an endocrinous cascade orchestrating the intimate interactions between Sertoli cells and germ cells and may operate as indispensable defensive mechanism in response to testicular IR stress. Future studies in this field would shed light on this complicated pathogenesis.