**2.2.1 Maternal syndrome of preeclampsia**

Placenta has the ability to synthesize several molecules, including mediators of inflammation and angiogenic factors, whose expression appears to be regulated by oxygen pressure and by the presence of oxidative stress (Rusterholz et al., 2007; Redman & Sargent, 2009). The expression of these molecules appears to be affected in PE; placental hypoxia/reperfusion and placental oxidative stress seems to be involved in this regulation, however, other modulators may contribute to that expression, such as genetic and immunological factors.

Some studies state that PE induces changes in the placental expression of tumor necrosis factor (TNF)-α, increasing this and other pro-inflammatory cytokines (Hung et al., 2004), and interleukin (IL)-6 (Bowen et al., 2005); however, there are conflicting results (Rusterholz et al., 2007).

Placenta seems to be the main source of placental growth factor (PlGF) and soluble vascular endothelial growth factor receptor (sVEGFR)-1, during pregnancy. A change in placental function may, therefore, interfere with the synthesis of these angiogenic/anti-angiogenic

Umbilical Cord Blood Changes in Neonates from a Preeclamptic Pregnancy 275

recognized that placenta has an important role in the protection and development of the fetus, promoting feto-maternal exchanges which are essential to a normal pregnancy. On the other hand, it is also recognized that in PE there are changes in placental development (Pijnenborg et al., 2006; Young et al., 2010), which can compromise the feto-maternal exchange, limiting fetal development, and trigger a maternal and fetal response to adapt

Angiogenic factors have been subject of intensive research in recent years, as they appear to be involved in the aetiology of PE. Several studies show a decrease in the concentration of PlGF (Polliotti et al., 2003; Levine et al., 2004) and an increase in circulating levels of sVEGFR-1 (McKeeman et al., 2004; Levine et al., 2004) in PEc women. Nevertheless, there is some controversy regarding the concentration of VEGF in pregnant women with PE (Simmons et al., 2000; McKeeman et al., 2004). Since sVEGFR-1 is an antagonist of PlGF and VEGF, there is a reduction of the effects of these factors, i.e., a change in angiogenesis and in endothelial function (Luttun & Carmeliet, 2003). The anti-angiogenic effect in pregnant women with PE seems to disappear after delivery (Maynard et al., 2008; Myatt & Webster, 2009), strengthening the involvement of placental factors in PE. VEGF plays an important role in vascular development, especially at placenta level, but also induces NO and prostaglandins synthesis, which are mediators of vasodilation (Myatt & Webster,

The processes of vasculogenesis/angiogenesis are crucial for the development of uteroplacental circulation and placenta. In a study performed by our group (Catarino et al., 2009a), we observed a disturbance of the angiogenic/anti-angiogenic factors in the maternal circulation in PE. PEc women had significantly higher levels of sVEGFR-1 (Fig. 2B) and VEGF values and significantly lower PlGF levels (Fig. 2A). This disruption in angiogenesis factors seems to be associated with placental dysfunction, since these factors are mainly

We also observed a positive correlation between levels of PlGF and maternal placental weight, in PEc pregnancy, which highlights the importance of PlGF in placental development (Catarino et al., 2009a). It is worthy to note that sVEGFR-1, an inhibitor of PlGF and VEGF, was significantly correlated with the amount of proteinuria, a marker of PE severity, suggesting an important role of sVEGFR-1 in the pathogenesis of PE (Catarino et al., 2009a). The abnormal development of the placenta in PE, reduces the placenta perfusion and may also contribute to the observed increase in the amounts of sVEGFR-1 and VEGF,

In cord blood samples of PEc cases, we observed a significant decrease in PlGF (Fig. 2C) and VEGF concentrations and a significant increase in the levels of sVEGFR-1 (Fig. 2D) (Catarino et al., 2009a). This disruption, particularly at values of PlGF and sVEGFR-1, seems to be an indirect indicator of the involvement of placental dysfunction in PE, since both are produced

The observed correlation between mother and child for sVEGFR-1 seems to indicate that the release of these factors by placenta, occurs both for the maternal and fetal circulation. However, the levels of sVEGFR-1 are higher in the blood of mothers, when compared with cord blood levels, which allows us to suppose that decidua, since it is able to secrete sVEGFR-1 (Lockwood et al., 2007), may also contribute for maternal levels of sVEGFR-1.

produced by the placenta (Kaufmann et al., 2004), during pregnancy.

since the tissue hypoxia regulates its production, stimulating it.

to these changes.

2009).

primarily in the placenta.

suggesting

factors. It has been shown that PEc placentas present an increased expression of sFlt1 (Gu et al., 2008), and a decreased expression of PlGF (Gu et al., 2008). These placental factors and cytokines appear to be released in maternal circulation, resulting in a generalized endothelial dysfunction, causing the multisystem complications of a PEc pregnancy (Rusterholz et al., 2007; Maynard et al., 2008) (Fig. 1).

Fig. 1. Possible mechanisms involved in the pathogenesis of preeclampsia
