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Emerging role of toll-like receptors signaling and its regulators in preterm birth: a narrative review

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Abstract

Introduction

Despite intensive research, preterm birth (PTB) rates have not decreased significantly in recent years due to a lack of understanding of the underlying causes and insufficient treatment options for PTB. We are committed to finding promising biomarkers for the treatment of PTB.

Methods

An extensive search of the literature was conducted with MEDLINE/PubMed, and in total, 151 studies were included and summarized in the present review.

Results

Substantial evidence supports that the infection and/or inflammatory cascade associated with infection is an early event in PTB. Toll-like receptor (TLR) is a prominent pattern recognition receptor (PRR) found on both immune and non-immune cells, including fetal membrane cells. The activation of TLR downstream molecules, followed by TLR binding to its ligand, is critical for infection and inflammation, leading to the involvement of the TLR signaling pathway in PTB. TLR ligands are derived from microbial components and molecules released by damaged and dead cells. Particularly, TLR4 is an essential TLR because of its ability to recognize lipopolysaccharide (LPS). In this comprehensive overview, we discuss the role of TLR signaling in PTB, focus on numerous host-derived genetic and epigenetic regulators of the TLR signaling pathway, and cover ongoing research and prospective therapeutic options for treating PTB by inhibiting TLR signaling.

Conclusion

This is a critical topic because TLR-related molecules and mechanisms may enable obstetricians to better understand the physiological changes in PTB and develop new treatment and prevention strategies.

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Acknowledgements

Special thanks are also extended to colleagues at the Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.

Funding

This article was supposed by the National Natural Fund Project (Grant No.19JSZ01, 81771619).

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Authors and Affiliations

  1. Department of Gynecology and Obstetrics, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China

    Ge Huang, Dan Yao, Xiaoli Yan, Ping Yan, Xiaoxia Chen & Dan Wang

  2. Department of Pharmacy, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China

    Mingyu Zheng

Authors
  1. Ge Huang
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  2. Dan Yao
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  3. Xiaoli Yan
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  4. Mingyu Zheng
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  5. Ping Yan
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  6. Xiaoxia Chen
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  7. Dan Wang
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Contributions

GH and DY wrote the manuscript. XY drew the figures and tables. MZ was in charge of the drug section of the discussion chapter. PY and XC were responsible for the examination and modification of the article. DW conceived the idea and critically reviewed the manuscript.

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Correspondence to Dan Wang.

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Huang, G., Yao, D., Yan, X. et al. Emerging role of toll-like receptors signaling and its regulators in preterm birth: a narrative review. Arch Gynecol Obstet 308, 319–339 (2023). https://doi.org/10.1007/s00404-022-06701-2

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