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Introduction. Fetal alcohol spectrum disorders (FASD) are a grouping of diagnoses that result from prenatal exposure to alcohol, and are the leading cause of neurodevelopmental disorders.^1,2 The prevalence of FASD in the U.S. is estimated to range from 11.3-50 per 1,000 children.³ Animal studies have found that the placenta is a primary source of angiogenic factors, and that establishment of a proper vascular network is imperative in the formation of the nervous system.^7,8,10,12 The placenta is the major source of these angiogenic factors including: Placental growth factor (Pgf) is a gene that codes for the angiogenic ligand, Placental growth factor (PLGF), that activates the pro-angiogenic vascular endothelium growth factor receptor 1 (VEGF-R1), which is present in the developing brain and the placenta.^7,11 Methods. Pregnant mice were injected with alcohol during gestation.⁷ Placental and fetal cortical samples were collected on GD20.⁷ Immunohistochemistry, using the endothelial cell marker, CD31, was used to visualize the cortical microvasculature changes.⁷ Cresyl violet-stained samples of the mouse placenta were used to study the vasculature changes.⁷ Samples of known alcohol-exposed human placentae were collected, and studied with the same techniques. ELISA and Western Blot techniques quantified PLGF and VEGF-R1 levels in the placenta and fetal brain.⁷ Oligodendrocyte precursor cell (OPC) migration was studied using Olig2-GFP labels attached to blood vessels of mice.¹² Results. Prenatal alcohol exposure impaired placental vasculature, which decreased the expression and distribution of PLGF, and VEGF-R1.^7,10 In the alcohol-exposed group of human placental samples, the villous density and vessel area were decreased when compared to the control.⁷ Repression of placental PLGF decreased fetal brain VEGF-R1 expression, which altered angiogenesis and cortical microvessel organization.⁷ Fetal mice demonstrated that prenatal alcohol exposure resulted in a loss of the normal radial organization of the vessels of the cortex; in fact, the greater the reduction of vascular density in the placenta, the more that the radial organization of the developing fetal brain was disrupted.⁷ Consequently, over-expression of placental Pgf in mice resulted in recovery of the angiogenic irregularities in the fetal brain.⁷ In addition, OPC migration in fetal mice was inhibited without the establishment of the proper vascular network.¹² Conclusions. Studies have found that alcohol decreases the expression of placental genes, and therefore proteins, that are imperative for normal angiogenesis of the placenta and the fetal brain. This, then, impairs the migration of neural cells, resulting in the abnormal cortical structures and cognitive deficits typically seen in FASD.

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