Growth factor concentrations and their placental mRNA expression are modulated in gestational diabetes mellitus: possible interactions with macrosomia.
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.
Grissa
Oussama
O
University of Burgundy, UPRES EA4183 Lipids and Cell Signaling, Faculty of Life Sciences, Dijon, France.
Yessoufou
Akadiri
A
Mrisak
Inès
I
Hichami
Aziz
A
Amoussou-Guenou
Daniel
D
Grissa
Abir
A
Djrolo
François
F
Moutairou
Kabir
K
Miled
Abdelhedi
A
Khairi
Hédi
H
Zaouali
Monia
M
Bougmiza
Iheb
I
Zbidi
Aabdelkarim
A
Tabka
Zouheir
Z
Khan
Naim A
NA
D000328:Adult; D016022:Case-Control Studies; D016640:Diabetes, Gestational / Q000097:blood*; D004815:Epidermal Growth Factor / Q000097:blood; D005260:Female; D005320:Fetal Macrosomia / Q000097:blood* / Q000175:diagnosis / Q000209:etiology; D016222:Fibroblast Growth Factor 2 / Q000097:blood; D013006:Growth Hormone / Q000097:blood; D006801:Humans; D007231:Infant, Newborn; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000032:analysis / Q000097:blood* / Q000235:genetics; D010920:Placenta / Q000737:chemistry / Q000378:metabolism*; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000097:blood; D014416:Tunisia; D015854:Up-Regulation / Q000502:physiology
D018972:Insulin-Like Growth Factor Binding Protein 3; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D016222:Fibroblast Growth Factor 2; D004815:Epidermal Growth Factor; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D020797:Receptor, Platelet-Derived Growth Factor beta