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

Abstract

Background: Gestational 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.

Methods: 30 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-beta were quantified by using RT-qPCR.

Results: The 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-beta, 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.

Conclusions: Our results demonstrate that growth factors might be implicated in GDM and, in part, in the pathology of macrosomia via materno-foeto-placental axis.

Figure 1

(a) Serum IGF-I concentrations, and (b) expression of placental mRNA of IGF-I and IGF-IR in gestational diabetic mothers and their babies. Serum IGF-I concentrations and mRNA expression by RT-PCR were assessed as described in the section of the methods. Values are means ± SD. NS = insignificant differences. n = 60 control mothers and babies; n = 60 gestational diabetic mothers and macrosomic babies.

Figure 2

(a) Serum IGF-BP3 concentrations and (b) expression of placental IGF-BP3 mRNA in gestational diabetic mothers and their babies. Serum IGF-BP3 concentrations and mRNA expression by RT-PCR were assessed as described in the section of the methods. Values are means ± SD. n = 60 control mothers and babies; n = 60 gestational diabetic mothers and macrosomic babies.

Figure 3

(a) Serum GH concentrations, and (b) expression of placental mRNA of GH and GHR in gestational diabetic mothers and their babies. Serum GH concentrations and mRNA expression by RT-PCR were assessed as described in the section of the methods. Values are means ± SD. n = 60 control mothers and babies; n = 60 gestational diabetic mothers and macrosomic babies.

Figure 4

(a) Serum EGF concentrations, and (b) expression of placental mRNA of EGF and EGFR in gestational diabetic mothers and their babies. Serum EGF concentrations and mRNA expression by RT-PCR were assessed as described in the section of the methods. Values are means ± SD. NS = insignificant differences. n = 60 control mothers and babies; n = 60 gestational diabetic mothers and macrosomic babies.

Figure 5

(a) Serum FGF-2 concentrations, and (b) expression of placental mRNA of FGF-2 and FGF-2R in gestational diabetic mothers and their babies. Serum FGF-2 concentrations and mRNA expression by RT-PCR were assessed as described in the section of the methods. Values are means ± SD. n = 60 control mothers and babies; n = 60 gestational diabetic mothers and macrosomic babies.

Figure 6

(a) Serum PDGF-B concentrations, and (b) expression of placental mRNA of PDGF-B and PDGFR-β in gestational diabetic mothers and their babies. Serum PDGF-B concentrations and mRNA expression by RT-PCR were assessed as described in the section of the methods. Values are means ± SD. n = 60 control mothers/babies; n = 60 gestational diabetic mothers/macrosomic babies.