Maternal Gestational Diabetes Mellitus increases placental and foetal lipoprotein-associated Phospholipase A2 which might exert protective functions against oxidative stress

Increased Lipoprotein associated Phospholipase A₂ (LpPLA₂) has been associated with inflammatory pathologies, including Type 2 Diabetes. Studies on LpPLA₂ and Gestational Diabetes Mellitus (GDM) are rare, and have focused mostly on maternal outcome. In the present study, we investigated whether LpPLA₂ activity on foetal lipoproteins is altered by maternal GDM and/or obesity (a major risk factor for GDM), thereby contributing to changes in lipoprotein functionality. We identified HDL as the major carrier of LpPLA₂ activity in the foetus, which is in contrast to adults. We observed marked expression of LpPLA₂ in placental macrophages (Hofbauer cells; HBCs) and found that LpPLA₂ activity in these cells was increased by Insulin, Leptin, and pro-inflammatory cytokines. These regulators were also increased in plasma of children born from GDM pregnancies. Our results suggest that Insulin, Leptin, and pro-inflammatory cytokines are positive regulators of LpPLA₂ activity in the foeto-placental unit. Of particular interest, functional assays using a specific LpPLA₂ inhibitor suggest that high-density lipoprotein (HDL)-associated LpPLA₂ exerts anti-oxidative, athero-protective functions on placental endothelium and foetus. Our results therefore raise the possibility that foetal HDL-associated LpPLA₂ might act as an anti-inflammatory Enzyme improving vascular barrier function.