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

TL;DR

This study examines placental monoamine oxidase A (MAO-A) activity in pregnancies affected by maternal overweight/obesity and gestational diabetes, finding subtle changes in substrate affinity for GDM but not for obesity.

Contribution

The study introduces a high-throughput fluorimetric assay to measure placental MAO-A activity and reveals how metabolic conditions affect its function.

Findings

Gestational diabetes mellitus (GDM) is associated with a modest increase in MAO-A substrate affinity (Km), but not with changes in maximum velocity (Vmax).

In metabolically healthy pregnancies, placental MAOA mRNA levels correlate with MAO-A catalytic capacity, but this relationship is absent in pregnancies with maternal overweight/obesity or GDM.

Abstract

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.

We developed a high-throughput fluorimetric assay using six concentrations of kynuramine as substrate to determine the kinetic parameters - maximum velocity (Vmax) and Michaelis affinity constant (Km) - 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.

Maternal OWO was not associated with changes in Vmax or Km, nor was GDM associated with changes in Vmax (all p>0.05). However, GDM was associated with a modest increase in Km (p=0.024), indicating reduced substrate affinity. In metabolically healthy pregnancies, placental MAOA mRNA levels correlated positively with Vmax (rp=0.68, p=0.001), while this relationship was absent in placentas from women with OWO and/or GDM (p>0.05).

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.

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