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VEGFA splicing: divergent isoforms regulate spermatogonial stem cell maintenance.

Kevin M Sargent1, Debra T Clopton1, Ningxia Lu1

  • 1Department of Animal Science, University of Nebraska-Lincoln, A224i Animal Science Building, 3940 Fair Street, Lincoln, NE 68583-0908, USA.

Cell and Tissue Research
|November 11, 2015
PubMed
Summary
This summary is machine-generated.

Vascular endothelial growth factor A (VEGFA) isoforms play critical roles in male fertility by regulating spermatogonial stem cells (SSC). Angiogenic VEGFA promotes SSC self-renewal, while antiangiogenic isoforms reduce SSC numbers, maintaining crucial stem cell homeostasis.

Keywords:
Self-renewalSpermatogoniaTestisVEGFA164VEGFA165b

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Area of Science:

  • Reproductive biology
  • Molecular endocrinology
  • Stem cell biology

Background:

  • Vascular endothelial growth factor A (VEGFA) is known for angiogenesis regulation.
  • VEGFA isoforms have divergent angiogenic and antiangiogenic roles.
  • Limited data exist on VEGFA's function in the mammalian testis.

Purpose of the Study:

  • Investigate the avascular functions of VEGFA isoforms in male fertility.
  • Determine the role of VEGFA in spermatogonial stem cell (SSC) maintenance.
  • Clarify the balance between angiogenic and antiangiogenic VEGFA isoforms in testicular homeostasis.

Main Methods:

  • Treatment of perinatal male mice with specific VEGFA isoforms (VEGFA165b and VEGFA164).
  • Assessment of seminiferous tubule colonization following transplantation of cells from treated donors.
  • Observation of KDR receptor expression on male germ cells.

Main Results:

  • Antiangiogenic VEGFA165b treatment reduced seminiferous tubule colonization by SSCs.
  • VEGFA165b may decrease SSC number via differentiation, cell death, or impaired formation.
  • Angiogenic VEGFA isoforms are hypothesized to support SSC self-renewal.

Conclusions:

  • VEGFA isoforms differentially regulate SSC number and function.
  • A balance between angiogenic and antiangiogenic VEGFA isoforms is essential for SSC homeostasis in vivo.
  • VEGFA plays a critical, previously underappreciated role in male fertility beyond angiogenesis.