Abstract 580: Apoptotic Signaling Is Augmented In Preeclampsia: An Adverse Impact On The Offspring

Abstract

Objective: Preeclampsia (preE), a syndrome of hypertension and proteinuria in pregnancy, is thought to be initiated with alterations of placental function. Hypoxia and oxidative stress can lead to placental apoptotic signaling, which pass the placental barrier and leave persistent defect in the circulation of the offspring that may predispose to a pathological response later in life. We assessed apoptotic signaling in placentas and umbilical cords from patients with or without preE. We also evaluated the pregnancy outcomes. Methods: In this study, we recruited 20 normal pregnant (NP) and 20 preE consenting patients in an IRB approved prospective study from Scott & White hospital, Temple, Texas. Inclusion criteria for determination of preE patients include blood pressure >140/90 and presence of proteinuria >300 mg of protein/24h urine. Samples of placenta and umbilical cord were collected from those subjects after deliveries. Apoptotic and stress signaling proteins; pro-apoptotic Bcl-2-associated X protein (Bax), anti-apoptotic Bcl-2 protein, caspase 9 and pro-inflammatory protein cyclooxygenase-2 (Cox-2) expression were assayed both by western blot and immunohistochemistry. The p38 mitogen-activated protein kinase (p38 MAPK) phosphorylation was evaluated by western blot. Comparisons were performed using ANOVA with Duncan’s post-hoc test. Results: The ratio of Bax/Bcl-2 expression (Placenta: 1.2 fold, Cord: 1.5 fold), Cox-2 (Placenta: 0.8 fold, Cord: 2.5 fold), Caspase 9 (Placenta: 1.5 fold, Cord: 1.8 fold), and p38 MAPK phosphorylation (Placenta: 1.5 fold, Cord: 1.7 fold) were up-regulated (p<0.05) in placental tissues and umbilical cords of preE compared to NP patients. We did follow up examination of the babies for both groups of patients to assess the pregnancy outcome. Average hospital stay for PreE babies were significantly longer than those of NP babies (3.4 vs 6.1). There were no complications has been reported for the NP babies. However, all of preE babies had multiple medical complications. Conclusions: Apoptotic signaling is augmented in preE which alters the intrauterine environment by modulating the pattern of hormonal signals and activating the detrimental cellular signaling that has been transported to the fetus.