Physiologic Concentrations of Magnesium and Placental Apoptosis

In Brief OBJECTIVE To identify the role of physiologic magnesium concentrations on the induction of placental apoptosis in vitro and test the anti-apoptotic action of antioxidants. METHODS Placental tissue was obtained from normal pregnancies after cesarean delivery. Placental explants were incubated with increasing concentrations of extracellular magnesium (range 0–2.0 mM). Placental apoptosis was evaluated by tissue morphology, DNA fragmentation, cytokeratin-18 neoepitope formation, and cleavage of plasminogen activator inhibitor type 2. RESULTS Physiologic concentrations of extracellular magnesium stimulated placental apoptosis. Magnesium stimulated apoptosis within the physiologic range (0.8–1.2 mM) (n = 6, P < .001) and was associated with cleavage of plasminogen activator inhibitor type 2 and cytokeratin-18 neoepitope formation. These data implicate caspase activation in the transduction of the magnesium-induced apoptotic signal. Therapeutic concentrations of vitamin C, vitamin E, and acetylcysteine (all at 25 μg/mL) inhibited DNA fragmentation and attenuated cleavage of plasminogen activator inhibitor type 2 and cytokeratin-18 neoepitope formation. CONCLUSION Magnesium-induced placental apoptosis is a potent mechanism of placental degeneration in vitro and may represent an important regulator of placental tissue dynamics in vivo. The ability of antioxidants to prevent magnesium-induced placental apoptosis implicates oxidation–reduction-dependent signaling events in this process. Furthermore, these findings provide a basis for further studies of antioxidants in mitigating the adverse effects of preeclampsia. Magnesium induces placental apoptosis as indicated by DNA laddering, cleavage of caspase-sensitive substrates, and tissue degeneration and is prevented by antioxidants.