Myo-Inositol Moderates Glucose-Induced Effects on Human Placental 13C-Arachidonic Acid Metabolism

Maternal hyperglycemia is associated with disrupted transplacental arachidonic acid (AA) supply and eicosanoid synthesis, which contribute to adverse pregnancy outcomes. Since placental inositol is lowered with increasing glycemia, and since myo-inositol appears a promising intervention for gestational diabetes, we hypothesized that myo-inositol might rectify glucose-induced perturbations in placental AA metabolism. Term placental explants (n = 19) from women who underwent a mid-gestation oral glucose-tolerance-test were cultured with C-13-AA for 48 h in media containing glucose (5, 10 or 17 mM) and myo-inositol (0.3 or 60 mu M). Newly synthesized C-13-AA-lipids were quantified by liquid-chromatography-mass-spectrometry. Increasing maternal fasting glycemia was associated with decreased proportions of C-13-AA-phosphatidyl-ethanolamines (PE, PE-P), but increased proportions of C-13-AA-triacylglycerides (TGs) relative to total placental C-13-AA lipids. This suggests altered placental AA compartmentalization towards storage and away from pools utilized for eicosanoid production and fetal AA supply. Compared to controls (5 mM glucose), 10 mM glucose treatment decreased the amount of four C-13-AA-phospholipids and eleven C-13-AA-TGs, whilst 17 mM glucose increased C-13-AA-PC-40:8 and C-13-AA-LPC. Glucose-induced alterations in all C-13-AA lipids (except PE-P-38:4) were attenuated by concurrent 60 mu M myo-inositol treatment. Myo-inositol therefore rectifies some glucose-induced effects, but further studies are required to determine if maternal myo-inositol supplementation could reduce AA-associated pregnancy complications.

Automated summary

Maternal hyperglycemia disrupts placental arachidonic acid metabolism, leading to adverse pregnancy outcomes. Myo-inositol shows potential in rectifying glucose-induced perturbations in placental AA metabolism. Further studies are needed to determine the effectiveness of maternal myo-inositol supplementation in reducing AA-associated pregnancy complications.