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首页> 外文期刊>Cell and Tissue Research >VEGFA splicing: divergent isoforms regulate spermatogonial stem cell maintenance
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VEGFA splicing: divergent isoforms regulate spermatogonial stem cell maintenance

机译：VEGFA剪接：异构亚型调节精原干细胞的维持

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摘要

Despite being well-known for regulating angiogenesis in both normal and tumorigenic environments, vascular endothelial growth factor A (VEGFA) has been recently implicated in male fertility, namely in the maintenance of spermatogonial stem cells (SSC). The VEGFA gene can be spliced into multiple distinct isoforms that are either angiogenic or antiangiogenic in nature. Although studies have demonstrated the alternative splicing of VEGFA, including the divergent roles of the two isoform family types, many investigations do not differentiate between them. Data concerning VEGFA in the mammalian testis are limited, but the various angiogenic isoforms appear to promote seminiferous cord formation and to form a gradient across which cells may migrate. Treatment with either antiangiogenic isoforms of VEGFA or with inhibitors to angiogenic signaling impair these processes. Serendipitously, expression of KDR, the primary receptor for both types of VEGFA isoforms, was observed on male germ cells. These findings led to further investigation of the way that VEGFA elicits avascular functions within testes. Following treatment of donor perinatal male mice with either antiangiogenic VEGFA165b or angiogenic VEGFA164 isoforms, seminiferous tubules were less colonized following transplantation with cells from VEGFA165b-treated donors. Thus, VEGFA165b and possibly other antiangiogenic isoforms of VEGFA reduce SSC number either by promoting premature differentiation, inducing cell death, or by preventing SSC formation. Thus, angiogenic isoforms of VEGFA are hypothesized to promote SSC self-renewal, and the divergent isoforms are thought to balance one another to maintain SSC homeostasis in vivo.
机译：尽管众所周知在正常和致瘤环境中均能调节血管生成，但血管内皮生长因子A（VEGFA）最近与男性生育力有关，即与精原干细胞（SSC）的维持有关。 VEGFA基因可以剪接成多种不同的同种型，其本质上是血管生成的或抗血管生成的。尽管研究证明了VEGFA的可变剪接，包括两种同工型家族类型的不同作用，但许多研究并未区分它们。关于哺乳动物睾丸中VEGFA的数据是有限的，但是各种血管生成的同工型似乎促进了生精索的形成并形成了一个梯度，细胞可以在该梯度上迁移。用VEGFA的抗血管生成同工型或血管生成信号抑制剂的治疗损害了这些过程。偶然地，在雄性生殖细胞上观察到了两种类型的VEGFA亚型的主要受体KDR的表达。这些发现导致对VEGFA在睾丸内引发血管功能的方式的进一步研究。用抗血管生成的VEGFA165b或血管生成的VEGFA164同工型治疗供体围产期雄性小鼠后，移植有VEGFA165b治疗的供体的细胞后，生精小管的定植较少。因此，VEGFA165b和可能的VEGFA的其他抗血管生成同工型通过促进过早分化，诱导细胞死亡或通过防止SSC形成来降低SSC数目。因此，假设VEGFA的血管生成同工型可促进SSC自我更新，并且发散的同工型被认为彼此平衡以维持体内SSC的体内稳态。

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