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Molecular Insights into Placental Pathology

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Guest Editor
Mother Infant Research Institute, Tufts Medical Center, Boston, MA 02111, USA
Interests: vascular biology of pregnancy
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Guest Editor
Mother Infant Research Institute, Tufts Medical Center, Boston, MA 02111, USA
Interests: pregnancy diagnostics

Special Issue Information

Dear Colleagues,

The placenta is a complex organ which develops de novo during pregnancy and serves a vital role in fetal protection. Specialized vasculature at the maternal–fetal interface (MFI) within the placenta mediates the transport of oxygen, nutrients, waste, and other compounds between the maternal and fetal circulatory systems. Molecular pathways that regulate the development of the placenta and the MFI have been discovered, but the molecular pathways that govern placental health and disease remain incompletely understood. Advancements in this field are critical for the development of early diagnostic indicators of placental dysfunction and placental diseases.

Supervised by Dr. Ana Correia-Branco and Dr. Mary Wallingford, we are pleased to announce this Special Issue of the International Journal of Molecular Sciences, titled “Molecular Insights into Placental Pathology”, which aims to collect papers that investigate molecular mechanisms underlying the development of disorders of the placenta. Studies delineating candidate diagnostic indicators, experimental in vitro and in vivo studies, animal models, nonanimal model systems, and clinical studies are welcome.

Topics of interest include but are not limited to the following:

  • The role of trophoblast cells and molecular pathways in implantation and placentation.
  • Multi-omic approaches to understanding the molecular basis of placental dysfunction, including pre-eclampsia and other obstetric complications.
  • Novel diagnostic tools and biomarkers for the early detection of placental disorders, with a focus on placental health and the maternal–fetal interface.

Dr. Mary Wallingford
Dr. Ana Correia-Branco
Guest Editors

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Keywords

  • placenta
  • trophoblast
  • implantation
  • obstetrics
  • pre-eclampsia
  • placentation
  • maternal–fetal interface
  • pregnancy health
  • placenta diagnostics

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Published Papers (3 papers)

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Research

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23 pages, 3064 KB  
Article
Immunohistochemical Analysis of Placental Tissue of Women Infected with SARS-CoV-2 During Pregnancy—A Prospective Clinical Study
by Marija Bicanin Ilic, Tamara Nikolic Turnic, Aleksandar Nikolov, Srdjan Mujkovic, Ivana Likic Ladjevic, Igor Ilic, Marija Spasojevic, Nikola Jovic, Jovana Joksimovic Jovic, Dejana Rakic, Begzudin Ahmetovic, Sara Rosic and Aleksandra Dimitrijevic
Int. J. Mol. Sci. 2025, 26(15), 7659; https://doi.org/10.3390/ijms26157659 - 7 Aug 2025
Viewed by 1097
Abstract
SARS-CoV-2 has an affinity for binding to the human Angiotensin-converting enzyme 2 (ACE2) receptor through cleavage and conformational changes at the S1–S2 boundary and the receptor binding domain of the spike protein, which is also the most variable part of SARS-CoV-2. This study [...] Read more.
SARS-CoV-2 has an affinity for binding to the human Angiotensin-converting enzyme 2 (ACE2) receptor through cleavage and conformational changes at the S1–S2 boundary and the receptor binding domain of the spike protein, which is also the most variable part of SARS-CoV-2. This study aimed to investigate the expression of Angiotensin-converting enzyme 2 (ACE2), spike protein, and CD68+ markers in placental tissue to demonstrate a possible correlation with the level of systemic oxidative stress biomarkers in patients who were infected with SARS-CoV-2 during pregnancy. A prospective clinical cohort study was designed to investigate the presence of CD68+ macrophages, ACE2, and spike proteins in placental tissue using immunohistochemical methods and to compare these results with oxidative stress from our previous study. Spike and CD68+ macrophages’ immunoreactivity were more pronounced in the placental tissue of patients from the SARS-CoV-2 group. Placental tissue spike protein and CD68+ immunoreactivity correlate with maternal and fetal Thiobarbituric Acid Reactive (TBARS) levels. This study has confirmed that spike protein expression in placental tissue is associated with the newborn’s stay in intensive neonatal care. Therefore, immunoreactivity analysis for the Spike antigen is important in detecting newborns at risk of early neonatal complications. Full article
(This article belongs to the Special Issue Molecular Insights into Placental Pathology)
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23 pages, 1185 KB  
Article
Potential Molecular Biomarkers of Preeclampsia—A Pilot Study
by Anna Romała, Eliza Matuszewska-Mach, Wiesław Markwitz, Maciej Brązert, Paulina Borysewicz, Dagmara Pietkiewicz, Jan Matysiak, Krzysztof Drews and Agata Szpera
Int. J. Mol. Sci. 2025, 26(13), 6149; https://doi.org/10.3390/ijms26136149 - 26 Jun 2025
Viewed by 1466
Abstract
Preeclampsia, one of the leading causes of maternal and fetal morbidity and mortality, affects approximately 3–5% of pregnancies worldwide. However, its etiology remains poorly understood. The aim of this study was to identify molecular markers of preeclampsia. Protein concentrations in blood and urine [...] Read more.
Preeclampsia, one of the leading causes of maternal and fetal morbidity and mortality, affects approximately 3–5% of pregnancies worldwide. However, its etiology remains poorly understood. The aim of this study was to identify molecular markers of preeclampsia. Protein concentrations in blood and urine were determined using the Bio-Plex Kidney Toxicity 1 assay Bio-Rad, Hercules, CA, USA followed by magnetic separation and flow cytometry. This study included 51 patients with preeclampsia and 25 healthy pregnant women. The results revealed that five out of the six serum biomarkers of kidney injury were elevated in the preeclampsia group compared to the control group (calbindin 1, clusterin, glutathione transferase pi (GSTP1), monocyte chemotactic protein 1 (MCP-1), and kidney injury molecule type 1 (KIM-1)). Additionally, the serum concentrations of calbindin 1, clusterin, GSTP1, and KIM-1 were significantly higher in both early-onset and late-onset preeclampsia compared to the control group. The analysis of urinary proteins showed that only the KIM-1 concentration was elevated in late-onset preeclampsia compared to the control group. These findings suggest that the calbindin 1, clusterin, GSTP1, KIM-1, and MCP-1 concentrations in maternal plasma could serve as potential biomarkers for monitoring kidney injury in preeclamptic women. This study provides a foundation for future research to explore novel biomarkers of preeclampsia and renal injury in pregnant women. Full article
(This article belongs to the Special Issue Molecular Insights into Placental Pathology)
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Review

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23 pages, 2424 KB  
Review
Molecular Insights into Human Placentation: From Villous Morphogenesis to Pathological Pathways and Translational Biomarkers
by Ioana Vornic, Radu Caprariu, Dorin Novacescu, Alina Cristina Barb, Victor Buciu, Adelina Băloi, Diana Szekely, Cristian Silviu Suciu, Catalin Dumitru, Raul Patrascu, Flavia Zara and Cristina Stefania Dumitru
Int. J. Mol. Sci. 2025, 26(19), 9483; https://doi.org/10.3390/ijms26199483 - 28 Sep 2025
Viewed by 1327
Abstract
Placental dysfunction underlies the major obstetric syndromes, including preeclampsia, fetal growth restriction, placenta accreta spectrum, pregnancy loss, and monochorionic twin complications. Recent molecular studies have revealed that dysregulated oxygen sensing, impaired angiogenic signaling, altered immune tolerance, and defective trophoblast fusion represent shared pathogenic [...] Read more.
Placental dysfunction underlies the major obstetric syndromes, including preeclampsia, fetal growth restriction, placenta accreta spectrum, pregnancy loss, and monochorionic twin complications. Recent molecular studies have revealed that dysregulated oxygen sensing, impaired angiogenic signaling, altered immune tolerance, and defective trophoblast fusion represent shared pathogenic pathways that converge across these disorders. Integrating morphological evidence with mechanistic data highlights how villous maldevelopment, shallow trophoblast invasion, and aberrant vascular remodeling translate into clinical disease. Advances in biomarker research have already transformed clinical care: the sFlt-1/PlGF ratio is now established in the prediction and management of preeclampsia, while placental proteins such as PAPP-A and PP13, nucleic acid signatures including cfDNA, cfRNA and miRNAs, and extracellular vesicle cargo show promising potential for early, non-invasive detection of placental pathology. Multi-omics approaches, particularly single-cell and spatial transcriptomics combined with proteomic and metabolomic profiling, are paving the way for composite diagnostic panels that capture the polygenic and multicellular nature of placental disease. This review synthesizes current knowledge of molecular mechanisms, histological correlates, and translational biomarkers, and outlines how precision obstetrics may emerge from bridging mechanistic discoveries with clinical applications. Full article
(This article belongs to the Special Issue Molecular Insights into Placental Pathology)
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