guanosine-triphosphate and Pre-Eclampsia

Preeclampsia is characterized by maternal hypertension and multi-organ injury. Elongation factor Tu GTP binding domain containing 2 (EFTUD 2) and the Pregnancy Zone Protein (PZP) seem to be important immunomodulatory factors in early gestation. Little is known about the role of EFTUD2 and PZP in disorders of late pregnancy like preeclampsia, HELLP syndrome and intrauterine growth restriction (IUGR). PZP, EFTUD2 and hCG expression was investigated by immunohistochemistry in the placenta of healthy pregnancies (n = 13), preeclampsia (n = 11), HELLP syndrome (n = 12) and IUGR (n = 8). Correlation analysis of protein expression was performed via Spearman correlation coefficient. The characterization of EFTUD2 and PZP expressing cells was evaluated by double-immunofluorescence. After cultivation of the chorion carcinoma cell line BeWo with hCG the expression of PZP and EFTUD2 was investigated by immunocytochemistry. PZP expression was significantly downregulated in the syncytiotrophoblast (ST) and extravillous trophoblast (EVT) of preeclampsia (ST: p 0.001, EVT:p = 0.019) and HELLP syndrome (ST: p = 0.004, EVT: p = 0.035). The expression of EFTUD2 was significantly lower in preeclampsia (ST: p = 0.003, EVT: p 0.001), HELLP syndrome (ST: p = 0.021, EVT: = 0.001, EVT: p = 0.001). EVTs were identified as EFTUD2 and PZP expressing cells by double-immunofluorescence. Stimulation of BeWo chorion carcinoma cells with hCG 1000 IU/mL for 48 h resulted in a significant upregulation of PZP expression (p = 0.027). Our results indicate that PZP and EFTUD2 might be involved in the development of placental dysfunction in preeclampsia and HELLP syndrome.

Topics: Carcinoma; Female; Fetal Growth Retardation; Guanosine Triphosphate; HELLP Syndrome; Humans; Peptide Elongation Factor Tu; Peptide Elongation Factors; Placenta; Pre-Eclampsia; Pregnancy; Pregnancy Proteins; Ribonucleoprotein, U5 Small Nuclear

Angiotensin II (ANG II) is a potent vasoconstrictor in isolated human placental cotyledons and may contribute to the regulation of fetoplacental perfusion. We have used quantitative in vitro receptor autoradiography to examine antagonist ((Sar1,Ile8)-[125I]ANG II) and agonist ligand ([125I]ANG II) binding sites in normal-term, preeclamptic and fetal (intrauterine) growth retarded pregnancies. A similar distribution of binding sites was demonstrated using both ligands, localized to blood vessels in placental villi. Binding density was inversely related to vessel size, being significantly greater on microvessels in distal regions of the villous tree than on proximal vessels in main stem villi. Binding sites exhibited the characteristics of the AT1 class of ANG II receptor, ligand binding being sensitive to dithiothreitol, completely inhibited by nonpeptide AT1 antagonists (Losartan, EXP3174 and SKF108566) and not inhibited by the AT2 antagonist (PD123319). Guanine nucleotides also inhibited [125I]ANG II binding and abolished the high affinity component of agonist inhibition of (Ser1,Ile8)-[125I]ANG II binding, indicating G protein coupling. The capacity and affinity of the binding sites were significantly lower in placentae from pregnancies complicated by preeclampsia and intrauterine growth retardation compared to that in normal-term controls. These differences were apparently not due to prior receptor occupancy by endogenous ligand, but may reflect activation of the placental renin-angiotensin system and receptor down-regulation. Locally generated ANG II, acting via AT1 receptors, may contribute to the regulation of fetoplacental blood flow and influence placental perfusion in preeclamptic and growth retarded pregnancies.

Topics: Angiotensin II; Autoradiography; Binding Sites; Blood Vessels; Female; Fetal Growth Retardation; Guanosine Triphosphate; Humans; In Vitro Techniques; Placenta; Pre-Eclampsia; Pregnancy; Receptors, Angiotensin