Abstract
ObjectiveTo investigate the placental proteome differences between pregnant women complicated with gestational diabetes mellitus (GDM) and those with normal glucose tolerance (NGT).MethodsWe used two-dimensional electrophoresis (2DE) to separate and compare placental protein levels from GDM and NGT groups. Differentially expressed proteins between the two groups were identified by MALDI-TOF/TOF mass spectrometry and further confirmed by Western blotting. The mRNA levels of related proteins were measured by realtime RT-PCR. Immunohistochemistry (IHC) was performed to examine the cellular location of the proteins expressed in placenta villi.ResultsTwenty-one protein spots were differentially expressed between GDM and NGT placenta villi in the tested samples, fifteen of which were successfully identified by mass spectrometry. The molecular functions of these differentially expressed proteins include blood coagulation, signal transduction, anti-apoptosis, ATP binding, phospholipid binding, calcium ion binding, platelet activation, and tryptophan-tRNA ligase activity. Both protein and mRNA levels of Annexin A2, Annexin A5 and 14-3-3 protein ζ/δ were up-regulated, while the expression of the Ras-related protein Rap1A was down-regulated in the GDM placenta group.ConclusionPlacenta villi derived from GDM pregnant women exhibit significant proteome differences compared to those of NGT mothers. The identified differentially expressed proteins are mainly associated with the development of insulin resistance, transplacental transportation of glucose, hyperglucose-mediated coagulation and fibrinolysis disorders in the GDM placenta villi.
Highlights
Gestational diabetes mellitus (GDM), defined as glucose intolerance that first occurs or is first identified during pregnancy [1], is a common disease that complicates 1–14% of all pregnancies [2]
Ethics Statement This study was approved by the research ethical committee of The First Affiliated Hospital of Sun Yat-sen University and written informed consent was provided by all volunteers
Clinical and laboratory data were compared between pregnant women complicated with gestational diabetes mellitus (GDM) and normal glucose tolerance (NGT)
Summary
Gestational diabetes mellitus (GDM), defined as glucose intolerance that first occurs or is first identified during pregnancy [1], is a common disease that complicates 1–14% of all pregnancies [2]. GDM has negative effects on the mother and the offspring in both short and long term. Women with GDM have a higher risk for developing additional complications during pregnancy, and are more likely to suffer from type-2 diabetes following pregnancy [3,4]. Offspring of GDM mothers have higher morbidity of adverse infant outcomes, and have an increased risk of diabetes, obesity, and cardiovascular disease in their adult life [5,6]. Metabolic dysfunctions in GDM, such as hyperglycemia, hyperinsulinemia, and dyslipidemia, can induce structural and functional abnormalities of the placenta villi [9,10,11]
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