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sFlt-1/PlGF and beyond: angiolymphatic-associated signatures and emerging biomarkers in placental pathology

2025/01/01 by Seetu Palo, Mishu Mangla, Rohini Motwani · 1 voice
Biochemistry, Genetics and Molecular Biology · Medicine · #Angiogenesis and VEGF in Cancer #Lymphatic System and Diseases #Pregnancy and preeclampsia studies

paper · doi:10.1530/vb-25-0009

openalex publication_date 2025/01/01 · openalex created_date 2025/11/28 · openalex updated_date 2026/07/08

Abstract

The placenta is a highly vascularised organ that depends on tightly regulated angiolymphatic networks to sustain normal fetal growth and maternal adaptation to pregnancy. Disruption of these pathways contributes to major obstetric complications, including preeclampsia, fetal growth restriction, gestational diabetes, and stillbirth. In recent years, advances in molecular pathology and high-throughput technologies have identified a spectrum of angiogenic, lymphangiogenic, and endothelial biomarkers that provide mechanistic insights and hold translational promise. Among these, vascular endothelial growth factors (VEGF-A, VEGF-C, VEGF-D), placental growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFlt-1), angiopoietins, podoplanin, and lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1) have emerged as key regulators. Differential expression of these markers in placental tissue, maternal circulation, and extracellular vesicles has been correlated with disease severity, placental morphology, and adverse neonatal outcomes. Despite growing evidence, clinical application is limited by methodological heterogeneity, gestational age-specific variability, and incomplete understanding of lymphatic involvement in placental physiology. This review synthesises current knowledge on angiolymphatic biomarkers in the placenta, highlighting their role in vascular development, disease pathogenesis, and potential as diagnostic and prognostic tools. Future research integrating molecular assays, imaging modalities, and systems biology approaches is essential to standardise biomarker panels and translate them into clinically meaningful strategies for maternal-fetal medicine.

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