Placental and maternal sFlt1/PlGF expression in gestational diabetes mellitus

Abstract

Gestational diabetes mellitus (GDM) and preeclampsia (PE) are both characterized by endothelial dysfunction and GDM women have higher incidence of PE. The placenta plays a key role in PE pathogenesis but its contribution to PE during GDM remains unclear. Herein, we compared placental and maternal blood anti-angiogenic soluble fms-like tyrosine kinase-1 (sFlt1) and pro-angiogenic Placental Growth Factor (PlGF) expressions in GDM and GDM-PE pregnancies compared to controls (CTRL) and PE cases. Electrochemiluminescence immunoassays showed a significantly higher maternal blood sFlt1/PlGF values in GDM-PE relative to CTRL and GDM pregnancies. We reported that placental PlGF gene expression was significantly decreased in GDM, PE and GDM-PE relative to CTRL. However, PlGF protein levels were significantly increased in GDM and GDM-PE relative to CTRL and PE placentae. Finally, sFlt1 gene expression was significantly increased in PE relative to CTRL, GDM and GDM-PE placentae. In contrast, sFlt1 protein expression was significantly decreased in GDM-PE relative to CTRL, GDM and PE placentae. Finally, higher sFlt1/PlGF ratio in GDM-PE maternal blood suggest that sFlt1 overproduction is related to PE onset also in GDM pregnancies even though characterized by a less severe endothelial dysfunction in terms of angiogenic biomarkers.

Figure 1

Maternal Blood PlGF, sFlt1 and sFlt1/PlGF ratio in CTRL, GDM, GDM-PE and PE pregnancies. (a) PlGF and (b) sFlt1, (c) sFlt1/PlGF ratio relative to fold increases and (d) boxplot of calculated sFlt1/PlGF ratios in CTRL, GDM, GDM-PE and PE patients as assessed by Elecsys methodology. Statistical significance has been considered as p < 0.05. ^#P < 0.05 versus CTRL; *P < 0.05 versus GDM; ^§P < 0.05 versus PE; ^{^}P < 0.05 versus GDM-PE.

Figure 2

PlGF and sFlt1 gene and protein expression levels in CTRL, GDM, GDM-PE and PE placentae. (a) mRNA and (b) protein expression of PlGF in CTRL, GDM, GDM-PE and PE placentae; (c) mRNA and (d) protein expression of sFlt1 in CTRL, GDM, GDM-PE and PE placentae. Statistical significance has been considered as p < 0.05. ^#P < 0.05 versus CTRL; *P < 0.05 versus GDM; ^§P < 0.05 versus PE; ^{^}P < 0.05 versus GDM-PE.