Ovary

Thrombospondin and Vascular Endothelial Growth Factor are Cyclically Expressed in an Inverse Pattern During Bovine Ovarian Follicle Development

Abstract
Angiogenesis does not normally occur in most adult tissues. However, in the ovary, there are cyclical vascular changes including angiogenesis that involve the interaction of numerous cytokines and growth factors. Angiogenic processes are regulated by a balance between pro- and anti-angiogenic factors. The purpose of this study was to determine the expression of the anti-angiogenic thrombospondin family and pro-angiogenic vascular endothelial growth factor (VEGF) in various sizes of healthy bovine follicles. Ovaries were collected from slaughterhouse animals and healthy follicles were sorted based on size (<0.5cm - small, 0.5-1.0cm - medium, >1.0cm - large). Thrombospondin protein levels were significantly higher in small follicles. Immunohistochemistry confirmed the granulosa layer as the primary area within the follicle involved in TSP generation, and that small follicles had the highest proportion of immunopositive cells. TSP-1 and -2 mRNA levels were significantly higher in small follicles than either medium or large follicles. TSP co-localized with CD36 on granulosa cells (GC) in the follicle and in cultured cells. In contrast to TSP, VEGF expression increased during growth and development of the follicle. FSH stimulated GC expression of TSP, while LH had no effect. In summary, TSP-1 and -2 were coordinately expressed in the extravascular compartment of the ovary during early follicle development. VEGF was inversely expressed, with expression increasing as follicles developed. Regulated expression and Localization of these proteins suggests that they may be involved in regulating growth and development of the follicle in a novel fashion.

Key words: Ovary • Follicle • Follicular development • Granulosa cells • Growth factors

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