Molecular Regulation of Trophoblast Invasion in Placental Function and Pregnancy Disorders

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Reproductive Cells and Development".

Deadline for manuscript submissions: 15 January 2027 | Viewed by 979

Editor


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Guest Editor
Institute for Application of Nuclear Energy (INEP), University of Belgrade, Belgrade, Serbia
Interests: immunology; neuroimmunology; reproductive immunology; inflammation; autoimmunity; senescence; aging; T cells; trophoblast; extracellular vesicles

Special Issue Information

Dear Colleagues,

The precise development and control of invasive trophoblast cells stand as a cornerstone of successful human pregnancy. These specialized cells, originating from the blastocyst's trophectoderm, are responsible for anchoring the embryo, remodeling maternal spiral arteries, and establishing the vital interface between mother and fetus. The molecular orchestration of their invasion—a process that must be deep enough to secure the pregnancy yet precisely constrained to avoid pathology—remains one of the most critical and enigmatic areas of reproductive biology. 

Dysregulation of this process underlies severe pregnancy disorders, with insufficient invasion linked to preeclampsia and fetal growth restriction, while excessive invasion is a hallmark of placenta accreta spectrum disorders. For decades, research has been hampered by limited access to early human placental tissue and a lack of physiologically relevant models. Today, the field is undergoing a transformative shift. Groundbreaking advances, such as the development of apical-out human trophoblast stem cell (hTSC) organoids that accurately mirror placental villous architecture, now offer unprecedented platforms to study trophoblast differentiation and invasion in vitro. 

This Special Issue, "Invasive Trophoblast Development and Regulation of Function," aims to capture this momentum. We seek to bring together cutting-edge research that illuminates the intrinsic and maternal regulators of trophoblast fate, from intracellular signaling cascades (e.g., STAT3, Wnt/β-catenin) and extracellular matrix interactions to emerging paradigms in mechanobiology and immune modulation. We welcome submissions that leverage novel stem cell models, omics technologies, and translational approaches to decode the principles of normal placentation and to forge new diagnostic or therapeutic strategies for pregnancy complications.

Dr. Mirjana Nacka-Aleksić
Guest Editor

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Keywords

  • trophoblast invasion
  • preeclampsia
  • placenta accreta
  • human trophoblast stem cells

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Published Papers (1 paper)

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Research

17 pages, 15101 KB  
Article
Decursinol Protects Against Lipopolysaccharide-Induced Placental Inflammation and Trophoblast Dysfunction via Mitochondrial Preservation and NLRP3 Inflammasome Inhibition
by Solji Lee, Hye-ji Lee, Jiha Shin, Sohee Lee, Jaeku Kang, Seok-Rae Park, Jong-Seok Kim, Jongdae Shin, Tae-Eun Jin, Nam-Kyung Lee, Ju-Young Park, Jeong Sig Kim, Nak Song Sung, Sung Ki Lee and Hwan-Woo Park
Cells 2026, 15(14), 1309; https://doi.org/10.3390/cells15141309 - 22 Jul 2026
Viewed by 425
Abstract
Inflammation-induced placental dysfunction is a major contributor to pregnancy complications. Activation of NF-κB and NLRP3 inflammasome pathways in the placenta is a key driver of this pathology. Decursinol, a natural coumarin derivative from Angelica gigas, possesses anti-inflammatory properties; however, its effect on placental [...] Read more.
Inflammation-induced placental dysfunction is a major contributor to pregnancy complications. Activation of NF-κB and NLRP3 inflammasome pathways in the placenta is a key driver of this pathology. Decursinol, a natural coumarin derivative from Angelica gigas, possesses anti-inflammatory properties; however, its effect on placental inflammation remains unclear. Therefore, in this study, we investigated the protective effects of decursinol against lipopolysaccharide (LPS)-induced placental inflammation and trophoblast dysfunction and explored the underlying molecular mechanisms. Decursinol significantly inhibited LPS-induced NLRP3 inflammasome activation and NF-κB/p65 signaling in Sw.71 human trophoblast cells, reducing interleukin-1β secretion and pro-inflammatory gene expression. It restored the trophoblast invasive capacity and preserved mesenchymal marker expression suppressed by LPS. It also improved the fetal and placental weights, restored the placental architecture, and attenuated placental NLRP3 inflammasome activation and cytokine expression in vivo. Mechanistically, decursinol preserved the mitochondrial homeostasis, reduced mitochondrial reactive oxygen species levels, and upregulated antioxidants and mitochondrial biogenesis-related gene levels, exerting effects comparable to those of mitochondria-targeted antioxidant Mito-TEMPO. These findings suggest that decursinol protects against LPS-induced trophoblast dysfunction and adverse pregnancy outcomes by preserving mitochondrial functions and suppressing NLRP3/NF-κB-mediated inflammation. Overall, our results highlight decursinol as a promising therapeutic candidate for inflammation-associated pregnancy complications. Full article
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