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Placental Angiogenesis in Mammals: A Review of the Regulatory Effects of Signaling Pathways and Functional Nutrients.

Normal placental development and proper angiogenesis are essential for fetal growth during pregnancy. Angiogenesis involves the regulatory action of many angiogenic factors and a series of signal transduction processes inside and outside the cell. The obstruction of placental angiogenesis causes fetal growth restriction and serious pregnancy complications, even leading to fetal loss and pregnancy cessation. In this review, the effects of placental angiogenesis on fetal development are described, and several signaling pathways related to placental angiogenesis and their key regulatory mediators are summarized. These factors, which include vascular endothelial growth factor (VEGF)-VEGF receptor, delta-like ligand 4 (DLL-4)-Notch, Wnt, and Hedgehog, may affect the placental angiogenesis process. Moreover, the degree of vascularization depends on cell proliferation, migration, and differentiation, which is affected by the synthesis and secretion of metabolites or intermediates and mutual coordination or inhibition in these pathways. Furthermore, we discuss recent advances regarding the role of functional nutrients (including amino acids and fatty acids) in regulating placental angiogenesis. Understanding the specific mechanism of placental angiogenesis and its influence on fetal development may facilitate the establishment of new therapeutic strategies for the treatment of preterm birth, pre-eclampsia, or intrauterine growth restriction, and provide a theoretical basis for formulating nutritional regulation strategies during pregnancy.