Placental monoamine oxidase A activity in pregnancies complicated by maternal overweight/obesity and gestational diabetes mellitus

Introduction The human placenta is a major site of metabolic transformation, synthesizing and catabolizing a wide range of bioactive compounds and thereby contributing to pregnancy success. Monoamine oxidase (MAO) is an important component of placental catabolic systems, catalyzing the oxidative deamination of biogenic monoamines, including serotonin and catecholamines. Methods We developed a high-throughput fluorimetric assay using six concentrations of kynuramine as substrate to determine the kinetic parameters - maximum velocity (V max ) and Michaelis affinity constant (K m ) - of MAO activity in human placental tissue. Pharmacological experiments with selective MAO-A and MAO-B inhibitors identified MAO-A as the sole catalytically active MAO isoform in human term placenta. We applied the assay to placental samples from 93 women to assess whether maternal overweight/obesity (OWO) and/or gestational diabetes mellitus (GDM) are associated with changes in placental MAO-A kinetic parameters, and to examine the relationship between placental MAOA mRNA levels and MAO-A catalytic capacity. Results Maternal OWO was not associated with changes in V max or K m , nor was GDM associated with changes in Vmax (all p>0.05). However, GDM was associated with a modest increase in K m ( p =0.024), indicating reduced substrate affinity. In metabolically healthy pregnancies, placental MAOA mRNA levels correlated positively with V max (rp=0.68, p=0.001), while this relationship was absent in placentas from women with OWO and/or GDM ( p >0.05). Conclusions Our findings suggest no alterations in placental monoamine catabolism in pregnancies complicated by maternal OWO, but indicate possible subtle changes in those complicated by GDM. The positive correlation between placental MAOA expression and MAO-A catalytic capacity in metabolically healthy pregnancies supports the use of MAOA mRNA levels as a proxy for MAO-A catalytic activity under physiological conditions. However, metabolic disturbances may disrupt this coupling, underscoring the value of the standardized kinetic assay described here as a robust tool for future studies of placental MAO-A function.