CASPASES, DNA FRAGMENTATION, AND OXIDATIVE STRESS: IMPLICATIONS FOR THE PATHOGENESIS OF PREECLAMPSIA AND RELATIONSHIP WITH THE MATERNAL RISK FACTORS AND PERINATAL OUTCOME.

For preeclampsia (PE), no specific etiological factor has been defined until now. This study focused on the implication of some apoptotic and lipid peroxidation markers in PE. In addition to malondialdehyde (MDA) measurement in the serum, the MDA, caspases-8, -9 activities and % DNA fragmentation were measured in fifty human term normal and PE placentas. In vitro MDA formation was assessed in relation to time and the presence of prooxidants (FeCh, low dose of ascorbate) and the antioxidant a- tocopherol. The MDA, % DNA fragmentation and caspase-9 activity were significantly increased in PE than control women. The serum MDA was significantly elevated in PE women delivered by cesarean section (C.S.) than vaginally delivered PE women. The addition of 0.5 mM Fe2+, 0.1 mM ascorbate caused increase production of MDA in PE than normal placentas (P 0.05). Vitamin E (100 µM) caused significantly lower inhibition of in vitro lipid peroxidation in PE placentas. The % DNA fragmentation and caspase-9 activity were related to the severity of the PE (ANOVA test). They could differentiate between PE and control women with 100%, 88% sensitivity and 100%, 96% specificity respectively. Caspases -8 and/or -9 activity positively correlates with the maternal age and negatively correlates with neonatal and placental weights. Conclusion: In preeclampsia, the placenta represents a considerable source of the elevated circulating MDA. The enhanced apoptosis correlates with the maternal age and perinatal outcome.