Screening of differentially expressed proteins from syncytiotrophoblast for severe early-onset preeclampsia in women with gestational diabetes mellitus using tandem mass tag quantitative proteomics

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.

Placental and maternal sFlt1/PlGF expression in gestational diabetes mellitus

“…GDM itself is a risk factor for PE and viceversa 25 – 29 . However, the relationship between pro-/anti-angiogenic factors and PE in women with GDM has been poorly explored 30 – 32 . From a physiopathological point of view, we expected GDM-PE to behave similarly to PE.…”

Association of Proteins Modulating Immune Response and Insulin Clearance during Gestation with Antenatal Complications in Patients with Gestational or Type 2 Diabetes Mellitus

“…Further functional analysis suggested that GDM is caused by oxidative stress, cell migration, angiogenic disorder, etc. [35].…”

A Critical Review of Proteomic Studies in Gestational Diabetes Mellitus

“…However, two studies are aimed at investigating adverse fetal outcomes, which selected GDM with macrosomia [33] or GDM with childhood obesity [35] as disease groups. Another study intended to identify biomarkers for one of the GDM-associated complications (early-onset PE) [40], which selected GDM as control groups. Additionally, one study is aimed at comparing GDM with NGT in obese pregnant women [43].…”

“…GDM is a complex complication affecting both maternal and fetal health. Several studies used specimens associated with fetomaternal communication, such as placental tissue (villi) [28,36], syncytiotrophoblast [40], and umbilical venous plasma [33,35,39,44]. These samples could provide key proteins for understanding the pathogenesis and progression of GDM, especially for GDM-related maternal complications and adverse fetal outcomes.…”

“…Second, peripheral blood and urine exosome samples were also drawn at the same time with diagnosis and used to identify biomarkers for precision diagnosis or classification [ 29 , 31 , 41 , 45 ]. Third, placental tissues, umbilical blood, omental adipose tissues, abdominus skeletal muscle tissue, and colostrum whey were obtained during or after delivery and used to identify markers for the pathogenesis of GDM or fetal outcomes [ 28 , 30 , 33 – 36 , 39 , 40 , 43 , 44 , 46 ].…”