Magnesium regulates hypoxia-stimulated apoptosis in the human placenta

Apoptosis (programmed cell death) in the human placenta is likely to play a major role in determining the structure and function of that organ. Fetal growth restriction (FGR) has been shown to be associated with increased lev els of placental apoptosis. Altered regulation of apoptosis may play an imp ortant pathophysiological role in FGR. As reduced placental perfusion and r educed oxygenation are features of FGR, one aim of this study was to determ ine the effects of hypoxia on apoptotic activity, as assessed by DNA ladder ing, of placental tissue in vitro. In addition, levels of placental apoptos is may be affected by pharmacological agents routinely used in obstetric pa tient management. Thus an additional aim of this study was to determine the effects of several relevant pharmacological agents on the levels of DNA la ddering during in vitro incubation of human placentae under hypoxic conditi ons. Incubation of normal placental explant tissue at 37 degrees C for 1-2 h under hypoxic conditions significantly increased placental DNA laddering compared with that in non-incubated tissue, whereas levels of DNA laddering during incubation for up to 2 h under normoxic conditions were not signifi cantly higher than those in non-incubated tissue. The DNA laddering activit y of placental explants after 2 h of incubation under hypoxic conditions wa s significantly increased with increased concentrations of magnesium, but r emained unchanged by the inclusion of pethidine, aspirin, nifedipine, dexam ethasone, heparin or indomethacin in the incubation mixture. These results suggest that hypoxia may stimulate apoptotic activity in cultured human pla cental tissues, and that hypoxia-stimulated placental apoptosis may be furt her increased by increasing the extracellular magnesium concentration.