Luteal angiogenesis and its control

Angiogenesis, the formation of new blood vessels from preexisting ones, is critical to luteal structure and function. In addition, it is a complex and tightly regulated process. Not only does rapid and extensive angiogenesis occur to provide the corpus luteum with an unusually high blood flow and support its high metabolic rate, but in the absence of pregnancy, the luteal vasculature must rapidly regress to enable the next cycle of ovarian activity. This review describes a number of key endogenous stimulatory and inhibitory factors, which act in a delicate balance to regulate luteal angiogenesis and ultimately luteal function. In vitro luteal angiogenesis cultures have demonstrated critical roles for fibroblast growth factor 2 (FGF2) in endothelial cell proliferation and sprouting, although other factors such as vascular endothelial growth factor A (VEGFA) and platelet-derived growth factor were important modulators in the control of luteal angiogenesis. Post-transcriptional regulation by small non-coding microRNAs is also likely to play a central role in the regulation of luteal angiogenesis. Appropriate luteal angiogenesis requires the coordinated activity of numerous factors expressed by several cell types at different times, and this review will also describe the role of perivascular pericytes and the importance of vascular maturation and stability. It is hoped that a better understanding of the critical processes underlying the transition from follicle to corpus luteum and subsequent luteal development will benefit the management of luteal function in the future.