The glycocalyx (GCX) is present on the luminal surface of endothelial cells, released from the endothelium upon injury or inflammation, and is a marker of endothelial damage [1]. GCX functions as an important barrier between the blood, interstitial space, and tissues, as well as a regulatory interface. GCX comprises proteoglycans, glycoproteins, and glycolipids [1]. Proteoglycans consist of core proteins (e.g., syndecans and glypicans) with covalently bound glycosaminoglycan side chains (e.g., heparan sulfate and chondroitin sulfate) [2], [3].

The placental glycocalyx is present on the syncytiotrophoblast (STB) brush border of the human placenta (facing the maternal blood) and is in direct contact with the maternal blood in the intervillous space [3]. STB-GCX may have a variety of functions, including regulation of the permeability and transport mechanisms of STB [3]. Although the exact physiological function of the abundant STB-GCX on the surface of the placental STB remains unclear, we consider that STB-GCX may maintain blood circulation homeostasis by inhibiting thrombus formation in the intervillous space. This assumption is supported by the report that GCX on the vascular endothelium suppresses blood coagulation within the vascular lumen and regulates the adhesion of platelets and neutrophils to the vascular lumen [4].

STB-GCX expression is decreased in preeclampsia (PE) [5], [6]. We suggest that damage to STB-GCX may cause pathological findings of PE, such as extensive intervillous thrombus formation and associated necrosis of peripheral villi [7]. The downregulation of Syndecan-1 (SDC-1), a major component of GCX, and decreased maternal blood levels of SDC-1 have also been reported before the onset of PE has been described [8], [9]. These studies suggest that STB-GCX is a major regulator of the uteroplacental circulation.

While SDC-1 may not capture the full complexity of the GCX, it serves as a widely accepted surrogate marker for GCX in many studies. As an illustrative example, immunofluorescence staining of SDC-1 in vascular tissues has been used to assess GCX status, and its expression has been shown to correlate with pathological progression [10].

Three-dimensional (3D) power Doppler sonography integrates the three-dimensional ultrasound with power Doppler. The application of Virtual Organ Computer-aided AnaLysis (VOCAL) software in 3D power Doppler volumes enables the quantification of blood flow and vascularity in target organs, which is reported to be clinically useful for detecting the construction and distribution of vessels and blood flow in various tumors and the placenta [11], [12], [13], [14], [15], [16], [17], [18], [19], [20]. Therefore, the Flow Index (FI) was measured using 3D vocal power Doppler sonography (3D-VPDS) technology to evaluate total placental blood flow (Supplemental Figure1), and we assessed the relationship between placental perfusion and STB-GCX expression.

Angiogenic factors such as placental growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFlt-1), and soluble endoglin (sEng) are thought to be deeply involved in the etiology of PE. Numerous previous reports have described elevated maternal blood levels of antiangiogenic factors such as sFlt-1 and sEng combined with decreased angiogenic factors such as PlGF, which is a consequence of placental insufficiency [21], [22], [23], [24]. Therefore, these angiogenic and antiangiogenic factors were adopted as biomarkers for placental malperfusion, and the relationship between these biomarkers and STB-GCX expression was analyzed in this study.

As the precise interaction between the expression of STB-GCX, FI measured using 3D-VPDS, and these angiogenic factors in PE remains unclear, we aimed to investigate these relationships, thereby assessing whether the expression of STB-GCX contributes to the maintenance of normal placental circulation and is involved in the pathological condition of PE induced by the disturbance of angiogenic factors and STB-GCX.