[266-POS]: Hyperglycemia impedes first trimester cytotrophoblast function via apoptotic signaling

Objectives Preeclampsia (preE) is a pregnancy disorder characterized by the de novo development of hypertension and proteinuria with multiple pathophysiologic triggers and mechanisms. Approximately 20% of the diabetic pregnant women develop preE. The mechanisms contributing to this effect is not well characterized. In a recent study, we show that hyperglycemia impairs cytotrophoblast (CTB) function via stress signaling. In the present study, we assess the apoptotic signaling mechanisms of excess glucose-induced CTBs dysfunction. Methods Human CTBs (Sw. 71) were treated with 0, 100, 200, 300 or 400 mg/dL glucose for 48 h. Some cells were pretreated with a p38 inhibitor (SB203580) or a peroxisome proliferator-activated receptor gamma (PPAR γ ) ligand (rosiglitazone). Some cells were treated with D-Mannitol to evaluate the osmotic effect. Thereafter, cell lysates were utilized to measure PPAR γ expression and p38 MAPK phosphorylation and apoptotic and stress signaling proteins; Bcl-2-associated X protein (Bax), anti-apoptotic Bcl-2 and caspase-3 and 9 and pro-inflammatory cyclooxygenase-2 (Cox-2) expression were assayed by western blot. Statistical comparisons were performed using analysis of variance with Duncan’s post hoc test. Results Both the p38 MAPK phosphorylation and PPAR γ expression were upregulated ( p 100 mg/dL glucose compared to basal (100 mg/dL). The expression of Bax/Bcl-2, Cox-2, caspase-3 and 9 were up-regulated ( p Conclusions Hyperglycemia induced the apoptotic signaling in CTBs by upregulating the Bax/Bcl2, and caspase-3 and 9 Cox-2 expression. The attenuation of hyperglycemia-induced upregulation of apoptotic and stress signaling proteins by SB203580 or rosiglitazone pretreatment suggests the involvement of apoptotic signaling mechanisms in CTBs dysfunction. Disclosures C. Cawyer: None. D. Leonard: None. N. Drever: None. R.R. Jones: None. S.R. Allen: None. M.R. Beeram: None. T.J. Kuehl: None. M.N. Uddin: None.