VEGFA splicing: divergent isoforms regulate spermatogonial stem cell maintenance

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• 作者：Kevin M. Sargent ; Debra T. Clopton ; Ningxia Lu…
• 关键词：VEGFA164 ; VEGFA165b ; Spermatogonia ; Testis ; Self ; renewal
• 刊名：Cell and Tissue Research
• 出版年：2016
• 出版时间：January 2016
• 年：2016
• 卷：363
• 期：1
• 页码：31-45
• 全文大小：2,217 KB
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• 作者单位：Kevin M. Sargent (1)
  Debra T. Clopton (1)
  Ningxia Lu (1)
  William E. Pohlmeier (1)
  Andrea S. Cupp (1)
  
  1. Department of Animal Science, University of Nebraska-Lincoln, A224i Animal Science Building, 3940 Fair Street, Lincoln, NE 68583-0908, USA
  
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Biomedicine
  Human Genetics
  Proteomics
  Molecular Medicine
  
• 出版者：Springer Berlin / Heidelberg
• ISSN：1432-0878

文摘

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.