Abstract
The cyclic nature of the capillary bed in the corpus luteum offers a unique experimental model to examine the life cycle of endothelial cells, involving discrete physiologically regulated steps of angiogenesis, blood vessel maturation and blood vessel regression. The granulosa cells and theca cells of the developing antral follicle and the steroidogenic cells of the corpus luteum produce and respond to angiogenic factors and vasoactive peptides. Following ovulation the neovascularization during the early stages of corpus luteum development has been compared to the rapid angiogenesis observed during tumor formation. On the other end of the spectrum, the microvascular endothelial cells are the first cells to undergo apoptosis at the onset of corpus luteum regression. Important insights on the morphology and function of luteal endothelial cells have been gained from a combination of in vitro and in vivo studies on endothelial cells. Endothelial cells communicate with cells comprising the functional unit of the corpus luteum, i.e., other vascular cells, steroidogenic cells, and immune cells. This review is designed to provide an overview of the types of endothelial cells present in the corpus luteum and their involvement in corpus luteum development and regression. Available evidence indicates that microvascular endothelial cells of the corpus luteum are not alike, and may differ during the process of angiogenesis and angioregression. The contributions of vasoactive peptides generated by the luteal endothelin-1 and the renin-angiotensin systems are discussed in context with the function of endothelial cells during corpus luteum formation and regression. The ability of two cytokines, tumor necrosis factor alpha and interferon gamma, are evaluated as paracrine mediators of endothelial cell function during angioregression. Finally, chemokines are discussed as a vital endothelial cell secretory products that contribute to the recruitment of eosinophils and macrophages. The review highlights areas for future investigation of ovarian microvascular endothelial cells. The potential clinical applications of research directed on corpus luteum endothelial cells are intriguing considering reproductive processes in which vascular dysfunctions may play a role such as ovarian failure, polycystic ovary syndrome (PCOS), and ovarian hyperstimulation syndrome (OHSS).
Highlights
The vascular endothelium of the mature ovarian follicle maintains the capacity for rapid growth in response to angiogenic signals elaborated during the periovulatory process
The contributions of vasoactive peptides generated by the luteal endothelin-1 and the renin-angiotensin systems are discussed in context with the function of endothelial cells during corpus luteum formation and regression
Reproductive Biology and Endocrinology 2003, 1 http://www.rbej.com/content/1/1/89 events occurring in the corpus luteum, the vascular endothelium of other tissues responds to extracellular signals during the physiologic processes of embryonic development and wound healing, and in the pathologic process of tumor angiogenesis
Summary
The vascular endothelium of the mature ovarian follicle maintains the capacity for rapid growth in response to angiogenic signals elaborated during the periovulatory process. The endothelial cell types differ in their expression of adhesion molecules [54], recruitment of leukocytes [56], and ability to form intercellular junctions [57] These in vitro and in vivo results, together with the selective presence of cytokeratinpositive cells in early corpus luteum development, provide evidence that cytokeratin-positive microvascular endothelial cells are morphologically and functionally different from the common cytokeratin-negative endothelial cell in the corpus luteum. A recent report by Tscheudschilsuren et al [73] on the expression of angiogenic factors and their receptors in cytokeratin-positive and -negative microvascular endothelial cells from the bovine corpus luteum shows that both types of microvascular endothelial cells produce VEGF mRNA. The involvement of steroid receptors and nitric oxide alone or in combination with vasoactive peptides and lipids, cytokines and/or chemokines are fertile fields of discovery using in vivo and in vitro approaches
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