Vascular Mimicry of Granulosa Cells: a New Concept of Corpeus Luteum Development?

So far, it was generally accepted that newly formed blood vessels are exclusively comprised of endothelial cells, and complemented by pericyte and myocyte recruitment during vessel maturation. Accordingly, participation of non-endothelial cells in the formation of blood vessels has rarely been suggested. Recently, evidence supporting the existence of tumour vessels lined by non-endothelial cells has emerged. Consequently, the concept of the inherent capacity of non-endothelial cells to behave like endothelial cells has been discussed for tumours, and this pathomechanism has been termed vascular mimicry. The corpus luteum is one of the most intensely vascularized tissues, and angiogenesis in the corpus luteum is more effective than in highly malignant tumours. Our results indicate active involvement of granulosa cells in luteal angiogenesis, and the aim of this study was to shed more light on this exciting prospect. The study was based on cultured granulosa cells isolated from the bovine ovary in different stages of follicle maturation. Morphology of angiogenic granulosa cells was studied by phase contrast, transmission electron and scanning electron microscopy. Expression of angiogenesis-regulating factors and their receptors was demonstrated by polymerase chain reaction (RT-PCR). Cultured granulosa cells underwent changes reminiscent of endothelial angiogenesis, i.e., migration, proliferation, differentiation and three-dimensional organization, and expressed angiogenesis-regulating factors and their receptors. Our results suggest a tight regulatory and structural association of endothelial and granulosa cells in luteal angiogenesis, suggesting physiological vascular mimicry in the ovary.