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Insufficient BMP8B–SULF2 signaling may contribute to preeclampsia by impairing extravillous trophoblast function

Year: 2026

Type: article

Abstract: Extravillous trophoblast (EVT) invasion is essential for placental development, and their dysregulation is a hallmark pathological feature of preeclampsia (PE). However, the underlying molecular mechanisms remain incompletely understood, limiting the development of clinically reliable biomarkers and therapeutic targets. Although bone morphogenetic protein 8B (BMP8B) has been reported to be highly expressed in placental trophoblasts, its potential role in early pregnancy placental development—particularly in EVT invasion—and in PE pathogenesis remains to be defined. Using RNA-seq analysis, RT–qPCR, Western blot, and immunostaining, we characterized the cell type-specific localization of BMP8B at the maternal–fetal interface and assessed its expression levels in preeclamptic placentas. Functional studies were performed using the immortalized EVT cell line HTR8/SVneo, primary human EVTs, and first-trimester villous explants to evaluate the role of BMP8B and its downstream target SULF2 in regulating EVT function. BMP8B is broadly expressed across multiple trophoblast subtypes, with its expression levels significantly downregulated in preeclamptic placentas. Recombinant BMP8B activates the PI3K-AKT pathway through ALK4/ACVR2B receptors and upregulates sulfatase 2 (SULF2) expression, thereby promoting EVT migration, invasion, and tube formation. Knockdown of endogenous BMP8B suppresses these EVT functional phenotypes, further supporting the pro-EVT functional role of BMP8B. Our findings establish the BMP8B–SULF2 signaling axis as a pivotal regulatory pathway governing EVT function. Disruption of BMP8B–SULF2 signaling in placental tissues may contribute to defective placentation and PE pathogenesis. Targeting BMP8B–SULF2 signaling axis may therefore offer new clinical avenues for early prediction and targeted intervention in PE.

Source: Biology Direct

DOI: 10.1186/s13062-026-01013-w