Differences in apoptotic susceptibility of cytotrophoblasts and syncytiotrophoblasts in normal pregnancy to those complicated with preeclampsia and intrauterine growth restriction.

Placental apoptosis is increased in vivo in preeclampsia (PE) and intrauterine growth restriction (IUGR). The cause and pathological implications of this phenomenon are unknown. This study considers the apoptotic susceptibility of villous trophoblasts from normal, PE, and IUGR pregnancies. Cultured cytotrophoblasts (CTs) and an in vitro model of syncytialization were used. CTs were isolated from term placentas of 12 normal, 12 PE, and 12 IUGR pregnancies. Apoptosis was determined by terminal dUTP nick-end labeling (TUNEL), Annexin V binding, and ADP:ATP ratios. Cells were stimulated with tumor necrosis factor-alpha/interferon-gamma or reduced oxygen (<5 KPa). For CTs, ADP:ATP <1 correlates with Annexin V binding. For normal pregnancy, tumor necrosis factor-alpha and depleted oxygen significantly increased TUNEL, Annexin V binding and ADP:ATP in CTs and syncytiotrophoblasts (STs). Spontaneous apoptosis was similar between groups for both cell types. After stimulation, TUNEL and Annexin V binding of CTs were significantly raised in PE and IUGR as compared with normal pregnancy. After oxygen reduction, ADP:ATP in CTs and STs were significantly elevated in IUGR. TUNEL was also increased in STs in PE after oxygen depletion and was significantly raised in STs from IUGR pregnancies after stimulation with both agonists. This is the first description of enhanced apoptosis in isolated villous trophoblasts in PE and IUGR. These intrinsic differences may represent an important factor in the pathophysiology of these conditions.