Fig. 7

Diagram summarizing the main effects of in utero alcohol exposure on the placenta and the fetal brain in mouse and human. a In the placenta, alcohol induced a decrease of PLGF expression in both mouse and human. This effect was associated with a decrease of VEGF-R1 levels in mouse. At a structural level, alcohol consumption altered the density of both villi and vessels in humans. The placental integrity was impacted by a decrease of the placental barrier marker ZO-1 and an increase of the energy metabolism marker MCT-1. b In the fetal brain, in utero alcohol exposure induced a disorganization of the cortical vasculature. Cortical VEGF-R1 levels were decreased, whereas PLGF was not detected. Recombinant human PLGF administered in the placenta reached the fetal brain. In utero repression of PGF transcription by shRNA mimicked the effects of alcohol on VEGF-R1 in the fetal brain while placental over-expression of the PGF gene induced macromorphic fetuses in the control group and rescued the effects of in utero alcohol exposure on vascular defects in the fetal brain. In human, vascular brain defects correlated with vascular placental defects.^m,h indicate the experiments performed in mouse and/or human; WB, Western blot approach; IHC, immunohistochemistry