Yael Pasternak MD1,2, Tal Biron-Shental MD1,2, Yael Einbinder MD2,3, Meital Ohana MSc3, Nissim Arbiv MD1,2, Sydney Benchetrit MD2,3, Tali Zitman-Gal PhD2,3
1Department of Obstetrics and Gynecology, Meir Medical Center, Kfar Saba, Israel
2Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
3Department of Nephrology and Hypertension, Meir Medical Center, Kfar Saba, Israelof… University….
Objective: Gestational diabetes mellitus class A2 (GDMA2) has short- and long-term effects on the mother and child, including placental abnormalities with endothelial damage and future cardiovascular disease. Trans-placental fatty acid and lipoprotein transport and turnover, including High Density Lipoproteins (HDL) might be involved in the pathophysiology related to GDMA2. The aim of this study is to assess changes in HDL quantity, qualitative composition and function among patients with GDMA2, the placentas and the neonates.
Study design: Thirty pregnant women (20 with GDMA2 and 10 with normal pregnancy (NP)) were recruited during admission for delivery. Blood samples were obtained from the parturients and umbilical cords, as well as placental tissue. Lipid profiles and
Apolipoprotein A-I (APOA1) levels were assessed in blood samples. HDL and its associated proteins: Paraoxonase-1 (PON1) and APOA1 function and expression were examined in maternal blood and placental tissue. An in vitro model of endothelial cells was used to evaluate the effect of HDL on cell migration.
Results: APOA1 (mg/dl) was lower in the maternal plasma of GDMA2 patients compared to NP (203±40 vs. 242±40; P=0.04). Maternal HDL release of APOA1 and PON1 was increased in GDMA2 compared to NP (1.97±1.1 vs. 1.0±0.18, P=0.027; 2.71±1.0 vs. 1.0±0.31, P<0.0001, respectively). Placental APOA1 and PON1 protein expression was lower in GDMA2 compared to NP (0.82±0.19 vs. 1±0.13, P=0.001; 0.63±0.24 vs. 1.03±0.37, P<0.0001, respectively). Lipid profile and APOA1 were similar in umbilical cord blood from GDMA2 and NP. HDL cell migration test in endothelial cells stimulated by the inflammatory factor TNFα was increased when cells were manipulated with GDMA2-HDL compared to NP-HDL (P<0.05).
Conclusions: GDMA2 affects plasma HDL composition and function. Interestingly, HDL changes typical to GDMA2 are observed in maternal and placental samples but not in cord samples. These results might imply a placental role in protecting the fetus and require further investigation.