Growth factor concentrations and their placental mRNA expression are modulated in gestational diabetes mellitus: possible interactions with macrosomia

Abstract

BackgroundGestational diabetes mellitus (GDM) is a form of diabetes that occurs during pregnancy. GDM is a well known risk factor for foetal overgrowth, termed macrosomia which is influenced by maternal hypergycemia and endocrine status through placental circulation. The study was undertaken to investigate the implication of growth factors and their receptors in GDM and macrosomia, and to discuss the role of the materno-foeto-placental axis in the in-utero regulation of foetal growth.Methods30 women with GDM and their 30 macrosomic babies (4.75 ± 0.15 kg), and 30 healthy age-matched pregnant women and their 30 newborns (3.50 ± 0.10 kg) were recruited in the present study. Serum concentrations of GH and growth factors, i.e., IGF-I, IGF-BP3, FGF-2, EGF and PDGF-B were determined by ELISA. The expression of mRNA encoding for GH, IGF-I, IGF-BP3, FGF-2, PDGF-B and EGF, and their receptors, i.e., GHR, IGF-IR, FGF-2R, EGFR and PDGFR-β were quantified by using RT-qPCR.ResultsThe serum concentrations of IGF-I, IGF-BP3, EGF, FGF-2 and PDGF-B were higher in GDM women and their macrosomic babies as compared to their respective controls. The placental mRNA expression of the growth factors was either upregulated (FGF-2 or PDGF-B) or remained unaltered (IGF-I and EGF) in the placenta of GDM women. The mRNA expression of three growth factor receptors, i.e., IGF-IR, EGFR and PDGFR-β, was upregulated in the placenta of GDM women. Interestingly, serum concentrations of GH were downregulated in the GDM women and their macrosomic offspring. Besides, the expression of mRNAs encoding for GHR was higher, but that encoding for GH was lower, in the placenta of GDM women than control women.ConclusionsOur results demonstrate that growth factors might be implicated in GDM and, in part, in the pathology of macrosomia via materno-foeto-placental axis.

Glycemic Variability and Mean Weekly Glucose in the Evaluation and Treatment of Blood Glucose in Gestational Diabetes Mellitus; Evidence for Lower Neonatal Complications

“…However complications seen on ultrasound were more frequent in the control group. The perinatal complications of GDM and glucose intolerance are well known in the literature [22][23][24][25][26]. Consitent with this, we found a significant difference between groups in terms of the number of neonates who suffered complications: 8 patients in the control group versus in intervention group.…”

Histomorphological Study of Placenta in Gestational Diabetes Mellitus

“…It was reported that vascular endothelial growth factor (VEGF), a potent stimulator of angiogenesis, has been implicated as one of the possible causes of angiogenesis in diabetic placenta, due to placental VEGF overexpression (Cohen et al, 2001;Grosfeld et al, 2002;Grissa et al, 2010).…”

Gestational Diabetes and the Offspring: Implications in the Development of the Cardiorenal Metabolic Syndrome in Offspring

“…Fetal adaptations to the increased concentration of glucose, amino acids, and lipids result in an excessive endogenous production of insulin and hyperplasia of β cells in the pancreas. Other anabolic hormones, such as insulin growth factor-1 (IGF-1), have been found to be elevated in the placenta of mothers with GDM [28]. In GDM, fetal growth is regulated by interactions between the nutritional status and anabolic hormones that seem to be responsible for macrosomia and adiposity in the fetus.…”