Placental BMP8B–SULF2 Signaling Defect Linked to Preeclampsia

A new study points to a signaling pathway in the placenta that may help explain why preeclampsia develops. Researchers report that bone morphogenetic protein 8B, or BMP8B, is significantly reduced in preeclamptic placentas, and that this loss appears to weaken the function of extravillous trophoblasts, the specialized cells that invade maternal tissue to build a healthy blood supply for the fetus.

Extravillous trophoblast invasion is essential for normal placental development, and its dysregulation is considered a hallmark pathological feature of preeclampsia. Yet the molecular mechanisms driving this failure remain incompletely understood, a gap that has limited the development of clinically reliable biomarkers and therapeutic targets. Although BMP8B was previously known to be highly expressed in placental trophoblasts, its role in early pregnancy placental development, particularly in trophoblast invasion, and in preeclampsia had not been clearly defined.

The team combined RNA sequencing, RT-qPCR, Western blotting, and immunostaining to map where BMP8B is produced at the maternal–fetal interface and to measure its levels in preeclamptic placentas. They found that BMP8B is broadly expressed across multiple trophoblast subtypes, but that its expression drops significantly in placentas affected by preeclampsia.

Functional experiments then tested what the protein actually does. Using the immortalized extravillous trophoblast cell line HTR8/SVneo, primary human extravillous trophoblasts, and first-trimester villous explants, the researchers showed that recombinant BMP8B promotes trophoblast migration, invasion, and tube formation. Conversely, knocking down the cells’ own BMP8B suppressed these functional behaviors, supporting its role as a positive regulator of trophoblast function.

The study also traced the signaling route downstream of BMP8B. The protein activates the PI3K-AKT pathway through ALK4 and ACVR2B receptors, and this activation upregulates sulfatase 2, known as SULF2. In this way, BMP8B appears to exert its pro-invasive effects at least partly through SULF2, defining what the authors describe as a BMP8B–SULF2 signaling axis governing extravillous trophoblast function.

Based on these results, the researchers propose that disruption of BMP8B–SULF2 signaling in placental tissues may contribute to defective placentation and to the pathogenesis of preeclampsia. Insufficient signaling, in this model, would leave extravillous trophoblasts less able to migrate and invade, undermining the remodeling of maternal vasculature that a pregnancy requires.

The authors suggest that targeting the BMP8B–SULF2 axis could offer new clinical avenues for early prediction and targeted intervention in preeclampsia. Such applications remain prospective: the findings establish a regulatory pathway and an association with preeclamptic placentas, and translating them into biomarkers or therapies would require further clinical validation.

It is also worth noting the scope of the evidence. The functional work relied on a trophoblast cell line, primary cells, and first-trimester tissue explants, which model early placental processes but do not by themselves demonstrate cause and effect in human pregnancies. The reduced BMP8B expression in preeclamptic placentas is an association observed in placental tissue, and the study does not establish when or how the downregulation occurs during pregnancy.

Nevertheless, the work adds a specific molecular candidate to the search for mechanisms behind preeclampsia, a condition long attributed to imperfect placental development but only partially explained at the mechanistic level. By connecting a placental growth factor family member to a defined receptor, pathway, and downstream target, the study offers a testable framework for future research into early detection and intervention.

The article was published open access in Biology Direct on 16 October 2026 and is currently available as a peer-reviewed accepted version that carries a permanent DOI and remains citable ahead of the final Version of Record.

Subject of Research: The role of BMP8B–SULF2 signaling in extravillous trophoblast function and preeclampsia

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

Article References: Liang, Y., Peng, Z., Ren, Z., Wu, K., Li, Y., Ban, Y., Meng, J., & Yan, J. (2026). Insufficient BMP8B–SULF2 signaling may contribute to preeclampsia by impairing extravillous trophoblast function. Biology Direct. https://doi.org/10.1186/s13062-026-01013-w

Image Credits: AI Generated

DOI: 10.1186/s13062-026-01013-w

Keywords: preeclampsia, placenta, BMP8B, SULF2, extravillous trophoblast, trophoblast invasion, PI3K-AKT pathway, placentation, pregnancy, molecular signaling, Insufficient, signaling