Role of Vascular endothelial growth factor (VEGF) and its receptors in avian ovarian follicle growth and differentiation

INTRODUCTION AND BACKGROUND INFORMATION

Angiogenesis is the process of forming new blood vessels from pre-existing capillaries, which plays pivotal roles in embryonic development, inflammation, and diabetic retinopathy. In particular, tumors secretes various growth factors (e.g., VEGF) to induce angiogenesis, which supplies the growing tumor with nutrients and oxygen, and allows for tumor metastasis. Vascular endothelial growth factor (VEGF), a potent and principal angiogenic factor, promotes the proliferation of endothelial cells by binding two receptors, VEGF-R1 (Flk) and -R2 (KDR). It has been previously shown that VEGF and its receptors are highly expressed in many types of tumors including ovarian cancer, suggesting that VEGF and its receptors may have a relationship with tumor formation (1, 3).

Prior work has linked angiogenesis and the female reproductive system by its influence on ovulatory cycles, follicle development, and the formation of the corpus luteum in the mammal. Moreover, these studies support the role of VEGF supporting follicle development by promoting proliferation and inhibiting apoptosis of granulosa cells (1,3) In addition, we hypothesize that an increase in vascularization occurs at the time of follicle selection. This increase in vascularization supports final growth and differentiation prior to ovulation. We expect that the increase in vascularization is the result of increasing expression of VEGF and its receptors. Therefore, by performing these studies and evaluating the expression of VEGF and its receptors in granulosa and theca cells from different stages of chicken follicles, I expect to elucidate some of the functions of angiogenesis involved with follicle selection and growth.

PROJECT OBJECTIVES

  • To identify the expression of VEGF and its receptors in granulosa and theca cells of chicken ovarian follicles.
  • To establish how expression of VEGF and its receptors in granulosa and theca cell expression changes as the follicles undergoes selection and final maturation.
  • To apply what I have been learning in my courses into a more hands-on experience by permitting me to become more familiar with a variety of cellular & molecular laboratory techniques.

SIGNIFICANCE OF THE PROJECT

By examining the expression of VEGF and its receptors at various stages of follicle development and cell types, we hope to gain a greater understanding of how the processes of follicular maturation/differentiation may be linked to angiogenesis.

Specifically, to understand why a greater vascularization is present on the mature/selected follicles, whereas decreased angiogenesis appears to occur in prehierachial/unselected follicles, and determine what role VEGF may play.

Since VEGF overexpression and that of its receptors are closely associated with tumorigenesis, this research might provide fundamental evidence to study ovarian cancer using the laying hen as the animal model.

LITERATURE CITED
1. Fraser, Hamish, and Colin Duncan. 2005. Vascular Morphogenesis in the Primate Ovary. Angiogenesis 8:101-116
2. Livak KJ & Schmittgen TD. 2001. Analysis of relative gene expression data using real-time quantitative PCR and the 2-∆∆Ct method. Methods 25: 402-408.
3. Qui, and Seager. 2012. Ovarian VEGF165b Expression Regulates Follicular Development, Corpus Luteum Function and Fertility. Reproduction 143:501-511