Molecular regulation and role of angiogenesis in reproduction

Abstract

Angiogenesis is an essential process for proper functioning of the female reproductive system and for successful pregnancy realization. The multitude of factors required for physiological angiogenesis and the complexity of regulation of their temporal-spatial activities contribute to aberrations in human fertilization and pregnancy outcomes. In this study, we reviewed the current knowledge of the temporal expression patterns, functions, and regulatory mechanisms of angiogenic factors during foliculogenesis, early implantation/placentation and embryo development, as well as recurrent spontaneous abortions. Angiogenic factors including vascular endothelial growth factors and angiopoietins have documented roles in the development of primordial follicles into mature antral follicles. They also participate in decidualization, which is accompanied by the creation of an extensive network of vessels in the stromal bed that support the growth of the embryo and the placenta, and maintain early pregnancy. During placentation angiogenic and angiomodulatory cytokines, T and B lymphocytes and macrophages affect angiogenesis in a context-dependent manner. Defects in angiogenesis at the maternal-fetal interface contribute to miscarriage in humans. The establishment of more polymorphisms in the genes involved in angiogenesis/vasculogenesis, and their pathological phenotype and expression could give opportunities for prediction, creating a therapeutic strategy, and treatment of diseases related to female reproductive health and problematic conception.

Activation of NF‐κB signaling pathway during HCG‐induced VEGF expression in luteal cells

“…In the ovary, VEGF is an important endocrine factor and involved in the normal and abnormal angiogenesis, especially in the newly formed corpus luteum (Fraser et al, ; Kaczmarek et al, ; Duncan et al, ; Zhang et al, , b, ; Kwik and Maxwell, ; Woad and Robinson, ; Jellad et al, ; Rizov et al, ). The follicles were ruptured after ovulation and the hypoxia was caused by accompanied bleeding and immature vasculatures (Nishimura and Okuda, ).…”

“…The present study showed VEGF mRNA expression was induced by HCG through activating NF-kB-mediated HIF-1a signaling in luteal cells, which was attenuated by NF-kB inhibitor PDTC and NF-kB siRNA, suggesting NF-kBmediated VEGF expression through the activation of HIF-1a signaling pathway could be a new molecular mechanism regulating the luteal VEGF-dependent angiogenesis in mammalian ovaries. In the ovary, VEGF is an important endocrine factor and involved in the normal and abnormal angiogenesis, especially in the newly formed corpus luteum (Fraser et al, 2000;Kaczmarek et al, 2005;Duncan et al, 2008;Zhang et al, 2011aZhang et al, , b, 2015Kwik and Maxwell, 2016;Woad and Robinson, 2016;Jellad et al, 2017;Rizov et al, 2017). The follicles were ruptured after ovulation and the hypoxia was caused by accompanied bleeding and immature vasculatures (Nishimura and Okuda, 2010).…”

“…Vascular endothelial growth factor (VEGF) is crucial for angiogenesis, which plays an important role in the formation of corpus luteum and the maintenance of luteal functions in mammals (Kaczmarek et al, 2005;Woad and Robinson, 2016;Rizov et al, 2017). Inhibition of VEGF will prevent luteal angiogenesis and progesterone secretion during the luteal phase, while excessive VEGF will also cause ovarian hyperstimulation syndrome during the luteal vascularization (Fraser et al, 2000;Duncan et al, 2008;Kwik and Maxwell, 2016;Jellad et al, 2017).…”

The role of CXC chemokine ligand 16 in physiological and pathological pregnancies

“…Angiogenesis is a crucially important process in a successful pregnancy, being involved in decidualization, implantation and embryo growth. 79 The role of chemokines in angiogenesis has gained increasing levels of attention. Current publications have mainly focused on the function of chemokines in tumor angiogenesis.…”

Studies on the Anti‐Angiogenic Activities of Wild and Cultivated Orostachys japonicus Extracts in Human Umbilical Vein Endothelial Cells

“…Angiogenesis is the formation of new blood vessels through physiological processes from preexisting vasculature. Under normal conditions, angiogenesis plays a significant role in growth JFDS-2019-0071 Submitted 1/15/2019, Accepted 5/5/2019 of embryos, wound healing, and ovarian function (Greaves & Ashcroft, 2013;Rizov, Andreeva, & Dimova, 2017). However, some studies have indicated that angiogenesis is also an important step in the development of tumor metastasis (Nishida, Yano, Nishida, Kamura, & Kojiro, 2006).…”