Neutralization of vascular endothelial growth factor antiangiogenic isoforms or administration of proangiogenic isoforms stimulates vascular development in the rat testis

Michelle M. Baltes-Breitwisch, Robin A. Artac, Rebecca C. Bott, Renee M. McFee, Jill G. Kerl, Debra T. Clopton, Andrea S. Cupp

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Vascular endothelial growth factor A (VEGFA) plays a role in both angiogenesis and seminiferous cord formation, and alternative splicing of the Vegfa gene produces both proangiogenic isoforms and antiangiogenic isoforms (B-isoforms). The objectives of this study were to evaluate the expression of pro- and antiangiogenic isoforms during testis development and to determine the role of VEGFA isoforms in testis morphogenesis. Quantitative RT-PCR determined that Vegfa-165b mRNA was most abundant between embryonic days 13.5 and 16 (E13.5 and 16; P<0.05). Compared with ovarian mRNA levels, Vegfa-120 was more abundant at E13-14 (P<0.05), Vegfa-164 was less abundant at E13 (P<0.05), and Vegfa-165b tended to be less abundant at E13 (P<0.09) in testes. Immunohistochemical staining localized antiangiogenic isoforms to subsets of germ cells at E14-16, and western blot analysis revealed similar protein levels for VEGFA-165B, VEGFA-189B, and VEGFA-206B at this time point. Treatment of E13 organ culture testes with VEGFA-120, VEGFA-164, and an antibody to antiangiogenic isoforms (anti-VEGFAxxxB) resulted in less organized and defined seminiferous cords compared with paired controls. In addition, 50 ng/ml VEGFA-120 and VEGFA-164 treatments increased vascular density in cultured testes by 60 and 48% respectively, and treatment with VEGFAxxxB antibody increased vascular density by 76% in testes (0.5 ng/ml) and 81% in ovaries (5 ng/ml) compared with controls (P<0.05). In conclusion, both pro- and antiangiogenic VEGFA isoforms are involved in the development of vasculature and seminiferous cords in rat testes, and differential expression of these isoforms may be important for normal gonadal development.

Original languageEnglish (US)
Pages (from-to)319-329
Number of pages11
JournalReproduction
Volume140
Issue number2
DOIs
StatePublished - Aug 1 2010

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ASJC Scopus subject areas

  • Reproductive Medicine
  • Embryology
  • Endocrinology
  • Obstetrics and Gynecology
  • Cell Biology

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