Novel Placental Biomarker Shows Predictive Potential for Spontaneous Preterm Labor

Bingbing Wang; Karl Seif; Jun Lei; Mary Mangione; Sifa Turan; E. Albert Reece; Irina Burd; Peixin Yang

doi:10.1055/a-2491-4391

American Journal of Perinatology, Inhaltsverzeichnis

Am J Perinatol 2025; 42(10): 1333-1343
DOI: 10.1055/a-2491-4391

Original Article

Novel Placental Biomarker Shows Predictive Potential for Spontaneous Preterm Labor

Bingbing Wang

¹Department of Obstetrics, Gynecology and Reproductive Sciences, University of Maryland School of Medicine, Baltimore, Maryland

,

Karl Seif

¹Department of Obstetrics, Gynecology and Reproductive Sciences, University of Maryland School of Medicine, Baltimore, Maryland

,

Jun Lei

¹Department of Obstetrics, Gynecology and Reproductive Sciences, University of Maryland School of Medicine, Baltimore, Maryland

,

Mary Mangione

¹Department of Obstetrics, Gynecology and Reproductive Sciences, University of Maryland School of Medicine, Baltimore, Maryland

,

Sifa Turan

¹Department of Obstetrics, Gynecology and Reproductive Sciences, University of Maryland School of Medicine, Baltimore, Maryland

,

E. Albert Reece

¹Department of Obstetrics, Gynecology and Reproductive Sciences, University of Maryland School of Medicine, Baltimore, Maryland

,

Irina Burd

¹Department of Obstetrics, Gynecology and Reproductive Sciences, University of Maryland School of Medicine, Baltimore, Maryland

,

Peixin Yang

¹Department of Obstetrics, Gynecology and Reproductive Sciences, University of Maryland School of Medicine, Baltimore, Maryland

› Institutsangaben

Abstract

Objective

Human parturition involves many events among mother, fetus, and placenta, and the initiation of these events is the consequence of activation of a series of endocrine and immune responses. Multiple underlying pathways account for the cascade of events that culminate in spontaneous preterm labor. In this study, we aimed to characterize these signaling pathways of placental origin at molecular levels.

Study Design

We used single-cell RNA-sequencing (sc-RNA-seq) analysis to probe transcriptional heterogeneity in human placenta delivered at preterm or term and then used RNA in situ hybridization (RNA-ISH) assay on formalin-fixed paraffin-embedded (FFPE) placental tissues to validate these results.

Results

By using sc-RNA-seq on villous cytotrophoblast (CTB) isolated from a preterm placenta, we found that signaling pathways implicated in the initiation of term or preterm labor including ferroptosis, kisspeptin (KISS1), and senescence were constitutively activated in distinct cellular clusters of these trophoblastic stem cells. RNA-ISH-based spatial gene expression profiling in FFPE tissues revealed that pregnancy-specific beta-1-glycoprotein 4 (PSG4), a potent molecular driver for cellular aging, was significantly increased in preterm placentas (N = 30) compared to their full-term counterparts (N = 9). Furthermore, PSG4 mRNA signals were predominantly detected in the villous syncytiotrophoblast and the discontinuous monolayer of CTB as well as the intervillous space where maternal blood circulates.

Conclusion

Our study provides strong support for PSG4 overexpression serving as a biomarker for pregnant women at risk for preterm delivery, which can allow for the development of timely and clinical preventive strategies.

Key Points

A sc-RNA-seq analysis on a preterm placenta identified multiple signaling pathways constitutively activated in distinct clusters of CTB.
RNA-ISH assay uncovered that the mRNA levels of PSG4, a molecular driver for cellular senescence significantly increased in preterm placentas compared to the term counterparts.
PSG4 mRNA signals were largely observed in the villous trophoblast as well as the intervillous space.

Keywords

placenta - PSG4 - senescence - biomarker - preterm birth

Volltext

Referenzen

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