The expression and activity of monoamine oxidase A, but not of the serotonin transporter, is decreased in human placenta from pre-eclamptic pregnancies

Abstract

Serotonin (5-HT) plays a pivotal role in pregnancy and a hyperserotonomic condition has been documented in pre-eclampsia. We have attempted to elucidate the possible participation of 5-HT as an aetiological factor in pre-eclampsia, by estimating the activity and expression of the 5-HT transporter (SERT) and monoamine oxidase A (MAO-A) in human placenta from full term normal (NG) and severe pre-eclamptic (PES) pregnancies. Uptake of 5-[1,2- 3H] hydroxytryptamine binoxalate (specific radioactivity, 30.4 Ci/mmol) was determined in placental brush border vesicles by a rapid filtration technique. 5-HT metabolism in placental homogenate was measured using a HPLC-ECD system. Expression of SERT and MAO-A was determined by Western blot, using specific antibodies against the human SERT and MAO-A in placental tissues obtained from NG and PES. Our results, showed no significant difference in 5-HT uptake between both groups. However, 5-HT metabolism was significantly lower in placental homogenates from PES than in NG placentas, with the pathological preparations showing no MAO-A activity against 5-HT during the first 60 min of incubation (87% and 5% of metabolism of 5-HT initially added, NG and PES respectively). Western blot analysis showed a similar expression of SERT in BBMV from NG and PES. However, unlike for normal pregnancies, the expression of MAO-A in placental homogenates from PES was found to be very low, or almost negligible. These findings confirm our previous results and suggest that the higher plasma free 5-HT levels observed in severe pre-eclampsia could be mainly due to a reduction in placental MAO-A expression and activity and are not limited by the expression and uptake of 5-HT into the placental tissue.