**2.1 New insights of molecule**

*Prediction of Maternal and Fetal Syndrome of Preeclampsia*

and the disease disappears once the placenta is delivered.

factor-beta receptor endoglin (CD105) [9, 11, 12] (**Figure 1**).

The placenta applies a significant factor in the pathogenesis of preeclampsia because the symptoms of PE can happen in molar pregnancy, which lacks a fetus,

Uteroplacental vascular insufficiency triggers fetus malnutrition and inadequate oxygen and nutrients. It is then identified clearly that the impact of such undernutrition condition seemingly causes coronary heart disease and hypertension in the future life [3–5]. It is easily noticed that the human placenta is only a temporary organ, but its effect on the fetus is protecting life. The correct function of the placenta necessitates the correct differentiation of the trophectoderm to set up a nutrition link between the embryo and mother [6]. In spite of numerous years of research, a holistic

comprehension molecular pathogenesis of preeclampsia remains unidentified.

The present study of pathogenesis of preeclampsia carried out by Christopher Redman and Ian Sergent is assumed to happen in two-phase series of unsuitable placental condition in the first and at the beginning of the second trimester, and it badly influences the rest of the pregnancy period [7, 8]. Anatomically, placental diagnosis uncovers that the most affected part of this illness is basal plate in which the cytotrophoblast (CBT) exists [9]. In preeclamptic condition, both interstitial CTB and endovascular invasion are not deep, and consequently, it triggers impaired vascular remodeling of the spiral arteries [10]. The next phase of preeclampsia is assumed maternity-related reactions to abnormal placentation as a consequence of endothelial dysfunction and an imbalance in circulating angiogenic/vasculogenic factors such as soluble vascular endothelial growth factor receptor-1 (VEGFR-1, sFlt-1), placental growth factor (PlGF), and the changing complete growth of

*In normal pregnancies, sFlt-1 and PIGF are in physiological angiogenic balance. Various factors and mediators influence the trophoblast invasion and placentation and in case of preeclampsia cause excessive production and liberation of sFlt-1 levels result in an unphysiological increase of the sFlt-1/PIGF ratio (angiogenic imbalance). Measurement of sFlt-1/PIGF ratio helps to identify women with preeclampsia and those who are likely to develop preeclampsia. ATI AA, angiotensin-converting enzyme autoantibodies. NK cells, natural killer cells.*

**2. Pathogenesis**

**22**

**Figure 1.**

There is substantial fact that a nonphysiological hypoxic environment subsequently in pregnancy could create such decontrol of angiogenic factors at the motherly embryonic connection. Lately, it has been indicated that the early preeclampsia is linked to anomalies regarding O2 sensing since preliminary preeclamptic placentas failed to control hypoxia-inducible factor 1- (HIF1-) alpha levels [13]. Incessant vulnerability in nonphysiological O2 levels in preeclampsia lowers vascular endothelial growth factor (VEGF), whereas sFlt-1 is really responsive. It is clearly accepted that produced sFlt-1 tied to VEGF and PlGF with huge similarity and consequently lowers their ability to link to their receptors [14]. The transformations act like an antiangiogenic treatment indicated in medical tests influencing similar medical symptoms such as angiogenesis dysfunction especially in vessels maturity, hypertension, proteinuria, and edema [14, 15]. Verlohren et al. [16] stated that the sFlt-1/ PlGF ratio is essential to recognize females at risk for delivery and is a convincing tool to differentiate between different types of pregnancy-related hypertensive illnesses. Females are classified preeclamptic, at gestational age <34 weeks; the circulating sFlt-1/PlGF ratio predicts adverse outcomes occurring within 2 weeks [17, 18]. However, the mechanisms by which placenta-derived sFlt-1 gains access to the maternal circulation remain unclear. Rajakumar et al. [19] report that the sFlt-1 protein is highly enriched in syncytial knots which is easily detach from the syncytiotrophoblast—a finding which is increased in preeclampsia. These multinucleated aggregates are metabolically active and are capable of de novo synthesis and may thus contribute to the maternal vascular injury in PE [19].

Moreover we revealed a deregulated expression of another molecule found in the bulk of changed molecules in PE: the matricellular CCN3 protein which lead to an imbalance in proliferation and migration of human trophoblast cells and could contribute to the shallow invasion of trophoblast cells into the decidual compartment and spiral arteries observed in preeclampsia [20–23]. In addition, in our recent publication, we could show that the cholesterol transporter ABCA1 is deregulated in early-onset preeclampsia resulted from placental hypoxia [24, 25]. These results focused on the importance of the maternal-fetal cholesterol transport for adequate development of the fetus.

Microarray datasets of basal plate biopsies of both normal placentation and PE (24–36 weeks) demonstrated novel observations indicating increased expression of the leptin receptor Siglec-6 and pappalysin (PAPP-A2), a metalloproteinase that cleaves insulin-like growth factor (IGF)-binding protein-5 (IGFBP-5), in PE placentas compared to controls. Overall, these results suggest alterations in important biological processes including pathways that are regulated by leptin and IGF signals [9].
