Several growth factors such as vascular endothelial growth factor (VEGF)-A and placental growth factor (PlGF) are involved in the placental vascular development. We investigated whether dysregulation in the VEGF family may explain the defective uteroplacental vascularization characterizing preeclampsia. We compared pregnancies complicated by early onset severe preeclampsia or intrauterine growth retardation to normal pregnancies. Maternal plasma, placentas, and placental bed biopsies were collected. The mRNA levels of VEGF-A, PlGF, and their receptors were quantified in placentas and placental beds. Levels of VEGF-A, PlGF, and soluble VEGF receptor (VEGFR) were assessed in maternal plasma. In compromised pregnancies, elevated levels of VEGF-A and VEGFR-1 mRNAs may reflect the hypoxic status of the placenta. On contrast, the membrane-bound VEGFR-1 was decreased in the placental bed of preeclamptic patients. Preeclampsia was associated with low levels of circulating PlGF and increased levels of total VEGF-A and soluble VEGFR-1. Free VEGF-A was undetectable in maternal blood. Immunohistochemical studies revealed that VEGF-A and PlGF were localized in trophoblastic cells. Altogether, our results suggest two different pathophysiological mechanisms associated with preeclampsia. The first one is related to an overproduction of competitive soluble VEGFR-1 that may lead to suppression of VEGF-A and PlGF effects. The second one is the down-regulation of its membrane bound form (VEGFR-1) in the placental bed, which may result in the defective uteroplacental development.

Early corticogenesis was studied in human embryos and early fetuses from Carnegie stages 16 to 22 (5-8 gestational weeks) by using immunohistochemistry for Reelin (Reln), calretinin (CR), and glutamic acid decarboxylase (GAD). A first population of Reln-positive cells appears in the neocortical anlage at stage 16 and increases in number at stages 17-18. At stages 19-20, a monolayer of horizontal CR- and GAD-positive, Reln-negative neurons forms in the preplate, whereas Reln-positive cells shift into a subpial position. Another cell class, the pioneer projection neuron, is CR-positive but GAD- and Reln-negative; pioneer cells contribute early corticofugal axons. Pioneer cells first appear below the monolayer at stage 20 and form a pioneer plate at stage 21. The cortical plate (CP) proper emerges at stage 21 and inserts itself within the pioneer plate, which is thus split into a minor superficial component and a larger deep component that presumably corresponds to the subplate. Initial CP neurons are radially organized and mostly CR-negative. Reln-positive cells remain consistently segregated from the pioneer cells and are thus not directly involved in preplate partition. Our data indicate that the neuronal composition of the human neocortical preplate is more complex than generally described and that various neurons participate in a sequence of events that precede the emergence of the CP.

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