The balance of proangiogenic and antiangiogenic VEGFA isoforms regulate follicle development

Renee M. McFee, Timothy G. Rozell, Andrea S. Cupp

Research output: Contribution to journalReview articlepeer-review

46 Scopus citations


Vascular endothelial growth factor A (VEGFA) has been extensively studied because of its role in follicular development and is a principal angiogenic factor essential for angiogenesis. Since vascularization of the theca layer increases as follicles progress in size through preantral and antral stages, VEGFA might influence follicle growth via the regulation of angiogenesis. However, VEGFA might also influence follicular development through nonangiogenic mechanisms, since its expression has been localized in nonvascular follicles and cells. Alternative mRNA splicing of eight exons from the VEGFA gene results in the formation of various VEGFA isoforms. Each isoform has unique properties and is identified by the number of amino acids within the mature protein. Proangiogenic isoforms (VEGFA-XXX) are encoded by exon 8a, whereas a sister set of isoforms (VEGFA-XXXB) with antiangiogenic properties is encoded by exon 8b. The antiangiogenic VEGFA-XXXB isoforms comprise the majority of VEGFA expressed in most tissues, whereas expression of the proangiogenic VEGFA isoforms is upregulated in tissues undergoing active angiogenesis. Although proangiogenic and antiangiogenic isoforms can now be distinguished from one another, many studies evaluating VEGFA in ovarian and follicular development up to now have not differentiated proangiogenic VEGFA from antiangiogenic VEGFA. Experiments from our laboratory indicate that proangiogenic VEGFA promotes follicle recruitment and early follicular development and antiangiogenic VEGFA inhibits these processes. The balance of proangiogenic versus antiangiognic VEGFA isoforms is thus of importance during follicle development. Further studies are warranted to elucidate the way that this balance regulates follicular formation and progression.

Original languageEnglish (US)
Pages (from-to)635-647
Number of pages13
JournalCell and Tissue Research
Issue number3
StatePublished - Sep 2012
Externally publishedYes


  • Follicle
  • Isoforms
  • Ovary
  • Vasculature
  • Vegfa

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Histology
  • Cell Biology


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