Placental and maternal sFlt1/PlGF expression in gestational diabetes mellitus

Anna Maria Nuzzo,Guido Menato,Giorgio Grassi,Paola Re,Laura Moretti,Domenica Giuffrida,Alessandro Rolfo

doi:10.1038/s41598-021-81785-5

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.

Highlights

Human pregnancy is characterized by a series of complex morphological and functional maternal adaptations to support fetal growth and development
Placental weight is significantly lower in Gestational Diabetes Mellitus (GDM)-PE and PE relative to CTRL groups but no significant differences are reported among GDM complicated by PE (GDM-PE) and GDM (p > 0.05)
The percentage of women with prepregnancy body mass index (BMI) ≥ 25 and ≥ 30 are significantly higher in GDM (p = 0.03 and p = 0.02), GDM-PE (p = 0.01 and p < 0.01) and PE (p = 0.01 and p = 0.02) groups relative to CTRL, while BMI at delivery is significantly increased in GDM-PE relative to CTRL (p < 0.01)

Summary

Introduction

Human pregnancy is characterized by a series of complex morphological and functional maternal adaptations to support fetal growth and development. A physiological rise in insulin resistance gradually starts during the second half of pregnancy and rapidly decreases after b irth[1] This physiological modification is designed to limit maternal glucose uptake in order to shunt an adequate nutrient supply to the growing fetus and it is believed to arise from increased maternal adiposity and the effects of placental hormones[2]. From a physiopathological point of view, we expected GDM-PE to behave to PE According to this hypothesis, the sFlt-1/ PlGF balance should be altered in GDM-PE patients, identifying GDM women at risk for PE development. We investigated placental and maternal blood sFlt1/PlGF expressions in GDM and GDM-PE pregnancies cases in order to explore a possible differential regulation of angiogenic molecules compared to CTRL and PE patients

Methods

Results

Discussion

Conclusion