ORCID

0000-0002-6811-4894 (Kimble), 0000-0002-0902-3159 (Wong), 0009-0009-9641-1325 (Doncel)

Document Type

Article

Publication Date

2025

DOI

10.3389/frph.2025.1587699

Publication Title

Frontiers in Reproductive Health

Volume

7

Pages

1587699

Abstract

Introduction: Preeclampsia (PE) is a complex multisystem disorder of pregnancy associated with abnormal placentation, vascular anomalies, and systemic inflammation and hypertension. Previous research assessing inflammatory triggers of the condition used plasma, amniotic fluid, or explant samples. Studies using placental tissue from either vaginal or cesarean deliveries are confined to semiquantitative analysis using subjective scoring methods and generally involve a small sample size.

Methods: In this study, we have quantified the expression of inflammatory mediators by immunohistochemical image analysis of archived placental tissues obtained from cesarean delivery of preeclamptic, chorioamnionitic, and normal pregnancies.

Results: Among the inflammatory mediators, we found a significant elevation in the expression of receptors of advanced glycation end products (RAGE) and two of its damage-associated molecular pattern proteins (DAMPs) and ligands, the high mobility group box protein HMGB1 and the calcium binding protein S100, in preeclamptic tissues as compared to normal placentas. In addition, we observed a significant increase in the master pro-inflammatory transcription factor, nuclear factor kappa B p65 subunit (NFκB), as well as non-significant increases in cyclooxygenase 2 (COX-2) and interleukin 8 (IL-8) in the PE group.

Conclusion: This study provides insight into the relationship of tissue inflammatory mediators with severe preeclampsia and the RAGE associated signaling complex, suggesting a pathogenic role for this pathway which has clinical implications for the understanding, diagnosis, and potential novel therapeutic approaches to the syndrome.

Rights

© 2025 Chandra, Kimble, Heim, Anderson, Wong, Thurman and Doncel.

This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International License (CC BY 4.0). The use, distribution or reproduction in other forums is permitted, provided the original authors and the copyright owners are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

Data Availability

Article states: "The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding author."

Original Publication Citation

Chandra, N., Kimble, T. D., Heim, K. R., Anderson, S. M., Wong, A. P., Thurman, A. R., & Doncel, G. F. (2025). Inflammatory mediators and the RAGE pathway in placental tissues of pregnancies complicated by severe preeclampsia. Frontiers in Reproductive Health, 7, Article 1587699. https://doi.org/10.3389/frph.2025.1587699

Additional Files
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