Abstract
BackgroundPrevious studies have revealed that women with gestational diabetes mellitus (GDM) have an increased risk of developing preeclampsia (PE). The possible reason is the abnormal lipid metabolism caused by GDM that leads to dysfunction of vascular endothelial cells and atherosclerosis, resulting in the onset of PE. However, studies focusing on the pathogenesis of PE in syncytiotrophoblast of GDM patients are lacking. This study aimed to compare differentially expressed proteins from syncytiotrophoblast between women with GDM and women with GDM with subsequently developed PE.MethodsSyncytiotrophoblast samples were obtained from pregnant women immediately after delivery. To explore the protein expression changes of syncytiotrophoblast that might explain the pathogenesis of PE in women with GDM, quantitative proteomics was performed using tandem mass tag (TMT) isobaric tags and liquid chromatography-tandem mass spectrometry. Bioinformatics analysis was performed to enrich the biological processes that these differentially expressed proteins were involved in.ResultsA total of 28,234 unique peptides and 4140 proteins were identified in all samples. Among them, 23 differentially expressed proteins were identified between patients with GDM and patients with GDM with subsequently developed PE. Therein, 11 proteins were upregulated and 12 proteins were downregulated. Two relative proteins (FLT1 and PABPC4) were independently verified using immunoblotting analysis. Bioinformatic results indicated that the onset of PE in patients with GDM is a multifactorial disorder, involving factors such as apoptosis, transcriptional misregulation, oxidative stress, lipid metabolism, cell infiltration and migration, and angiogenesis.ConclusionThese results indicated that the inadequacy of endometrium infiltration, angiogenic disorder, and oxidative stress in syncytiotrophoblast are more likely to occur in patients with GDM and may be the potential mechanisms leading to such patients secondarily developing severe early-onset PE.
Highlights
Previous studies have revealed that women with gestational diabetes mellitus (GDM) have an increased risk of developing preeclampsia (PE)
The results showed that Vascular endothelial growth factor receptor 1 (FLT1) was expressed at higher levels, while Polyadenylatebinding protein 4 (PABPC4) was expressed at lower levels in PE with GDM groups than in GDM groups (Fig. 2), suggesting that the immunoblotting results were in line with tandem mass tag (TMT) proteomics results
Bioinformatic results indicated that the onset of PE form GDM patients is a multifactorial disorder, involving in apoptosis, transcriptional misregulation, oxidative stress, cell infiltration and migration, angiogenesis, etc
Summary
Previous studies have revealed that women with gestational diabetes mellitus (GDM) have an increased risk of developing preeclampsia (PE). The possible reason is the abnormal lipid metabolism caused by GDM that leads to dysfunction of vascular endothelial cells and atherosclerosis, resulting in the onset of PE. Studies focusing on the pathogenesis of PE in syncytiotrophoblast of GDM patients are lacking. Early-onset PE is associated with abnormal placental function, mainly manifested in the insufficient invasion of the maternal myometrium by the trophoblast cells, which results in uterine spiral artery remodelling disorder and placental superficial implantation. Late-onset PE is associated with maternal predisposition to arterial diseases, developed due to interfering endothelial function by obesity, diabetes, lipid metabolism dysfunction, and inflammation [1, 6,7,8]
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