Maternal-fetal transport kinetics of manganese in perfused human placental lobule in vitro

Objective: There have been no detailed reports relating to maternal-fetal transport kinetics of manganese, an essential trace element in the human pregnancies, and hence we have attempted to study the transport kinetics of this trace element in the human placenta in vitro.Methods: Human placentae from normal uncomplicated pregnancies were collected postpartum. Manganese chloride solution (GFS Chem Inc., Columbus, OH), 10 times the physiological concentrations, along with antipyrine (Sigma Chem Co., St. Louis, MO) as reference marker were then injected as a single bolus (100 μl) into the maternal arterial circulation of perfused placental lobules and perfusate samples collected from maternal and fetal circulations over a period of five minutes. National Culture and Tissue Collection medium, diluted with Earles buffered salt solution was used as the perfusate and serial perfusate samples from fetal venous perfusate collected for a period of 30 min. Concentration of manganese in perfusate samples was assessed by atomic absorption spectrophotometry, while that of antipyrine was assessed by spectrophotometry. Transport kinetics of substances studied were computed using established permeation parameters.Results: Differential transport rates of manganese and antipyrine in 12 perfusions differed significantly for 25.75, 90% efflux fractions (ANOVA test, p < 0.05), while those of 10 and 50% efflux fractions were not significantly different between the study and reference substances. Transport fraction (TF) of manganese averaged 54.9% of bolus dose in 12 perfusions, whereas that of antipyrine averaged 89% of bolus dose, representing 61.80% of reference marker TF. The difference observed in TF values of manganese and antipyrine was statistically significant (Students t-test, p < 0.05). Pharmacokinetic parameters such as area under the curve, clearance, absorption rate, elimination rate of manganese compared to reference marker were significantly different (ANOVA test, p < 0.05) between the study and reference substances.Conclusions: Our studies show for the first time maternal-fetal transport kinetics of manganese in human placenta in vitro. Considering the restricted transfer of this essential trace element despite its small molecular weight, we hypothesize possibility of active transport of manganese across the human placental membrane. Further studies relating to manganese placental transport in "diabetic model" placental perfusions are in progress.