ArticlePloS one2020
Changes in pregnancy-related serum biomarkers early in gestation are associated with later development of preeclampsia.
Article in PloS one, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 29 citations in OpenAlex.
- Late-gestation mineralocorticoid receptor antagonism lowers maternal blood pressure and attenuates placental insufficiency induced by leptin in pregnant mice.American journal of physiology. Heart and circulatory physiology · 2026Article
- Adjunct Diagnostic Accuracy of Antigen-specific Interleukin-2 for Latent Tuberculosis Infection in Pregnancy.Open forum infectious diseases · 2026Article
- Sex-specific placental transcriptome alterations in late-onset preeclampsia reveal male-biased immune and metabolic dysregulation.Biology of sex differences · 2025Observational
- Heme oxygenase/carbon monoxide system affects the placenta and preeclampsia.Medical gas research · 2025Review
- Emerging Role of Leptin in Vascular and Placental Dysfunction in Preeclampsia.Arteriosclerosis, thrombosis, and vascular biology · 2025Review
- Molecular signatures of preeclampsia subtypes determined through integrated weighted gene co-expression network analysis and differential gene expression analysis of placental transcriptomics.Frontiers in cell and developmental biology · 2025Article
- Article
- Prediction of risk for early or very early preterm births using high-resolution urinary metabolomic profiling.BMC pregnancy and childbirth · 2024Article
- Exploring the ceRNA network involving AGAP2-AS1 as a novel biomarker for preeclampsia.Scientific reports · 2024Article
- Both endothelial mineralocorticoid receptor expression and hyperleptinemia are required for clinical characteristics of placental ischemia in mice.American journal of physiology. Heart and circulatory physiology · 2024Article
- Article
- Ceramides during Pregnancy and Obstetrical Adverse Outcomes.Metabolites · 2023Review
- Midgestation Leptin Infusion Induces Characteristics of Clinical Preeclampsia in Mice, Which Is Ablated by Endothelial Mineralocorticoid Receptor Deletion.Hypertension (Dallas, Tex. : 1979) · 2022Article
- Ferroptosis-related gene expression in the pathogenesis of preeclampsia.Frontiers in genetics · 2022Article
- Gestational Dating by Urine Metabolic Profile at High Resolution Weekly Sampling Timepoints: Discovery and Validation.Frontiers in molecular medicine · 2022Article
- Bioinformatics analysis combined with clinical sample screening reveals that leptin may be a biomarker of preeclampsia.Frontiers in physiology · 2022Article
- Early-pregnancy prediction of risk for pre-eclampsia using maternal blood leptin/ceramide ratio: discovery and confirmation.BMJ open · 2021Article
- Role of Gelatinases MMP-2 and MMP-9 in Healthy and Complicated Pregnancy and Their Future Potential as Preeclampsia Biomarkers.Diagnostics (Basel, Switzerland) · 2021Review
- Differences in expression of Peroxisome Proliferator-activated Receptor-γ in early-onset preeclampsia and late-onset preeclampsia.BMC research notes · 2020Article
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Authors and funding
25 authors at 5 institutions in 2 countries.
Funding
Abstract
backgroundPlacental protein expression plays a crucial role during pregnancy. We hypothesized that: (1) circulating levels of pregnancy-associated, placenta-related proteins throughout gestation reflect the temporal progression of the uncomplicated, full-term pregnancy, and can effectively estimate gestational ages (GAs); and (2) preeclampsia (PE) is associated with disruptions in these protein levels early in gestation; and can identify impending PE. We also compared gestational profiles of proteins in the human and mouse, using pregnant heme oxygenase-1 (HO-1) heterozygote (Het) mice, a mouse model reflecting PE-like symptoms.
methodsSerum levels of placenta-related proteins-leptin (LEP), chorionic somatomammotropin hormone like 1 (CSHL1), elabela (ELA), activin A, soluble fms-like tyrosine kinase 1 (sFlt-1), and placental growth factor (PlGF)-were quantified by ELISA in blood serially collected throughout human pregnancies (20 normal subjects with 66 samples, and 20 subjects who developed PE with 61 samples). Multivariate analysis was performed to estimate the GA in normal pregnancy. Mean-squared errors of GA estimations were used to identify impending PE. The human protein profiles were then compared with those in the pregnant HO-1 Het mice.
resultsAn elastic net-based gestational dating model was developed (R2 = 0.76) and validated (R2 = 0.61) using serum levels of the 6 proteins measured at various GAs from women with normal uncomplicated pregnancies. In women who developed PE, the model was not (R2 = -0.17) associated with GA. Deviations from the model estimations were observed in women who developed PE (P = 0.01). The model developed with 5 proteins (ELA excluded) performed similarly from sera from normal human (R2 = 0.68) and WT mouse (R2 = 0.85) pregnancies. Disruptions of this model were observed in both human PE-associated (R2 = 0.27) and mouse HO-1 Het (R2 = 0.30) pregnancies. LEP outperformed sFlt-1 and PlGF in differentiating impending PE at early human and late mouse GAs.
conclusionsSerum placenta-related protein profiles are temporally regulated throughout normal pregnancies and significantly disrupted in women who develop PE. LEP changes earlier than the well-established biomarkers (sFlt-1 and PlGF). There may be evidence of a causative action of HO-1 deficiency in LEP upregulation in a PE-like murine model.
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