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Author Spotlight: Modeling an Aspect of Preeclampsia in Female Mice Using Hypoxic Human Placenta-Derived Small Extracellular Vesicles
Published on: January 26, 2024
Serum proteins differentially expressed in early- and late-onset preeclampsia assessed using iTRAQ proteomics and
Chengcheng Tu1, Feng Tao1, Ying Qin2
1Department of Obstetrics and Gynecology, Maternal and Child Health Hospital Affiliated to Anhui Medical University, Hefei, Anhui, China.
Insights
Preeclampsia pathogenesis involves coagulation, lipid metabolism, and complement system abnormalities. Early-onset preeclampsia also shows placental injury, with identified serum proteins aiding diagnosis.
Area of Science:
- Proteomics
- Biochemistry
- Medical Science
Background:
- Preeclampsia poses significant risks to maternal and infant health globally.
- Investigating pathogenic mechanisms is crucial for understanding and managing preeclampsia.
- This study focuses on serum differentially expressed proteins (DEPs) in early-onset (EOPE) and late-onset preeclampsia (LOPE).
Purpose of the Study:
- To identify and compare DEPs in serum from patients with EOPE and LOPE versus healthy pregnant women.
- To elucidate the pathogenic mechanisms underlying EOPE and LOPE.
- To discover potential protein biomarkers for clinical diagnosis of preeclampsia subtypes.
Main Methods:
- Serum samples from EOPE, LOPE, and normal pregnancies were analyzed using quantitative proteomics (isobaric tags for relative and absolute quantitation) and liquid chromatography-tandem mass spectrometry.
- Bioinformatics analyses (Gene Ontology, Kyoto Encyclopedia of Genes and Genomes) were performed on DEPs (fold-change > 1.2, P < 0.05).
- Key protein candidates were validated using enzyme-linked immunosorbent assay (ELISA).
Main Results:
- EOPE group showed 70 DEPs (51 upregulated, 19 downregulated) compared to controls.
- LOPE group showed 24 DEPs (10 upregulated, 14 downregulated) compared to controls.
- DEPs in both groups were linked to coagulation cascade, complement system, and lipid metabolism; EOPE DEPs also related to placental development. Pregnancy-specific beta-1-glycoprotein 9 (PSG9) was downregulated in LOPE.
Conclusions:
- Pathogenesis of EOPE and LOPE involves coagulation, lipid metabolism, and complement activation.
- EOPE pathogenesis is further associated with increased placental injury.
- Identified serum proteins offer potential for clinical diagnosis and understanding preeclampsia mechanisms.
Background:
Preeclampsia remains a serious disorder that puts at risk the lives of perinatal mothers and infants worldwide. This study assessed potential pathogenic mechanisms underlying preeclampsia by investigating differentially expressed proteins (DEPs) in the serum of patients with early-onset preeclampsia (EOPE) and late-onset preeclampsia (LOPE) compared with healthy pregnant women.
Methods:
Blood samples were collected from four women with EOPE, four women with LOPE, and eight women with normal pregnancies, with four women providing control samples for each preeclampsia group. Serum proteins were identified by isobaric tags for relative and absolute quantitation combined with liquid chromatography-tandem mass spectrometry. Serum proteins with differences in their levels compared with control groups of at least 1.2 fold-changes and that were also statistically significantly different between the groups at P < 0.05 were further analyzed. Bioinformatics analyses, including gene ontology and Kyoto Encyclopedia of Genes and Genomes signaling pathway analyses, were used to determine the key proteins and signaling pathways associated with the development of PE and to determine those DEPs that differed between women with EOPE and those with LOPE. Key protein identified by mass spectrometry was verified by enzyme linked immunosorbent assay (ELISA).
Results:
Compared with serum samples from healthy pregnant women, those from women with EOPE displayed 70 proteins that were differentially expressed with significance. Among them, 51 proteins were significantly upregulated and 19 proteins were significantly downregulated. In serum samples from women with LOPE, 24 DEPs were identified , with 10 proteins significantly upregulated and 14 proteins significantly downregulated compared with healthy pregnant women. Bioinformatics analyses indicated that DEPs in both the EOPE and LOPE groups were associated with abnormalities in the activation of the coagulation cascade and complement system as well as with lipid metabolism. In addition, 19 DEPs in the EOPE group were closely related to placental development or invasion of tumor cells. Downregulationof pregnancy-specific beta-1-glycoprotein 9 (PSG9) in the LOPE group was confirmed by ELISA.
Conclusion:
The pathogenesis of EOPE and LOPE appeared to be associated with coagulation cascade activation, lipid metabolism, and complement activation. However, the pathogenesis of EOPE also involved processes associated with greater placental injury. This study provided several new proteins in the serum which may be valuable for clinical diagnosis of EOPE and LOPE, and offered potential mechanisms underpinning the development of these disorders.
