Date Published: January 26, 2017
Publisher: Public Library of Science
Author(s): Guo Yao, Yafang Zhang, Di Wang, Ruirui Yang, Hui Sang, Linlin Han, Yuexia Zhu, Yanyan Lu, Yeke Tan, Zhanping Shang, Kwang-Hyun Baek.
To investigate if the role of Cav-1 in GDM-induced macrosomia is through regulating AMPK signaling pathway in placenta.
We used diagnostic criteria of gestational diabetes mellitus (GDM) and macrosomia to separate and compare placental protein and mRNA levels from GDM with macrosomia group (GDMM), GDM with normal birth weight group (GDMN) and normal glucose tolerance (NGT) with normal birth weight group (CON). Western blotting was performed to examine differentially expressed proteins of caveolin-1 (Cav-1) and Adenosine monophosphate-activated protein kinase (AMPK) signaling pathway related proteins, including phosphorylated-AMPKα(Thr172), AMPKα, phosphorylated-Acetyl-CoA carboxylase(Ser79) (p-ACC(Ser79)), ACC and glucose transporter 1 (GLUT1) in placenta between the three groups. The mRNA levels of Cav-1, AMPKα, ACC and GLUT1 in placenta were measured by real time-PCR.
In the GDMM placenta group, both protein and mRNA levels of Cav-1 were down-regulated, while GLUT1 was up-regulated; the phosphorylation and mRNA levels of ACC and AMPKα were decreased, but total ACC protein levels were increased compared to both the GDMN (p<0.05) and CON groups (p<0.05). In GDMM placenta group, there was a significant negative correlation observed between neonatal birth weight (NBW) and protein expression levels of Cav-1, p-ACC(Ser79) and p-AMPKα(Thr172) (p<0.05), while positive relationship with ACC and GLUT1 protein levels. Besides, in GDMM group placental mRNA levels, NBW had a positive correlation with GLUT1 (p<0.05), while negative with Cav-1, AMPKα and ACC expression (p<0.05). Cav-1 protein expression was positively associated with p-AMPK and p-ACC (p<0.05), and negatively associated with GLUT1 (p<0.05). Interestingly, p-AMPK protein expression was closely related to p-ACC (p<0.05), but not with GLUT1. GDM-induced macrosomias have more severe inhibition of Cav-1 expression in placenta. Cav-1 is associated with placental glucose and fatty acid transport via the induction of AMPK signaling pathway and the reduction of GLUT1 signaling pathway to reverse GDM-induced macrosomia.
GDM, which is defined as a group of glucose and lipid metabolism disorders , severely threats fetal perinatal period and growth of offspring in the long term [2–4]. It is generally considered that the neonates born to diabetic mothers have an increased risk for macrosomia. Macrosomia is accompanied by more risks of dystocia, neonatal asphyxia, neonatal hypoglycemia and perinatal death. Besides, many studies confirme that GDM-induced macrosomia has the long term risk of diabetes, obesity and other metabolic dysfunctions later in life [5, 6].
GDM has generally been acknowledged as a serious pregnancy complication to harm the fetus. Recent studies reveal macrosomia has a obviously rising trend among GDM-induced adverse pregnancy outcomes [20, 21]. Interestingly, no effective reduction of prevalence of macrosomia is achieved, although the clinical treatment of GDM has been significantly improved [22–24]. Previous studies mainly focused on improving maternal glucose homeostasis due to lower concentration difference of maternal-fetal glucose [25–27]. Our results indicated that the birth weight of GDM group was still significantly higher than that of the NGT group, in spite of achieving the ideal goal of maternal glycemic control in the third trimester. Combined with the correlation analysis results, there is no doubt that GDM patients have a more important risk factor in the induction of macrosomia than maternal glucose levels.