2. Academic Validation
  3. Endoplasmic reticulum stress induces trophoblast pyroptosis via regulating CYLD during labor initiation

Endoplasmic reticulum stress induces trophoblast pyroptosis via regulating CYLD during labor initiation

  • Placenta. 2025 Jun 26:167:204-215. doi: 10.1016/j.placenta.2025.05.020.
Xiaolei Zhang 1,  Meitao Yang 2,  Dan Lv 3,  Yanling Zhang 4,  Yin Xie 5,  Mengzhou He 3,  Yao Fan 3,  Xufang Li 3,  Fatoumata Jallow 3,  Fanfan Li 3,  Dongrui Deng 6
Affiliations

Affiliations

  • 1 Department of Gynecology and Obstetrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Department of Gynecology and Obstetrics, Guizhou Provincial People's Hospital, Guizhou, China.
  • 2 Department of Gynecology and Obstetrics, Zhongnan Hospital, Wuhan University, Wuhan, China.
  • 3 Department of Gynecology and Obstetrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • 4 Department of Obstetrics and Gynecology, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, China.
  • 5 Department of Obstetrics, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • 6 Department of Gynecology and Obstetrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address: tjdengdongrui@126.com.
PMID: 40418867 DOI: 10.1016/j.placenta.2025.05.020
Abstract

Introduction: Preterm birth (PTB) presents significant risks to neonatal health, highlighting a deeper understanding of the mechanisms underlying labor initiation. Maternal-fetal interface inflammation and heightened endoplasmic reticulum stress (ERS) are associated with the onset of PTB, while the molecular mechanism remains unclear. This study investigates ERS levels in placental tissues from term and preterm pregnancies and examines the role of ERS and cylindromatosis (CYLD) in trophoblast Pyroptosis to reveal the mechanisms underlying PTB.

Methods: A total of 60 pregnant women were recruited and categorized into four groups: term labor (TL), term not in labor (TNL), preterm labor (PTL), and preterm not in labor (PTNL). Protein expressions of ERS and pyroptosis-related molecules, including CYLD, were assessed using Western blotting, immunohistochemistry, and immunofluorescence. IL-1β and IL-18 mRNA levels were quantified via Real-Time PCR. An in vitro inflammatory trophoblast model was established using LPS and ATP co-treatment. ERS modulation was achieved with Thapsigargin (TG) and Tauroursodeoxycholate (TUDCA).

Results: Elevated ERS and pyroptosis-related protein levels were observed in PTB-associated groups and the inflammatory trophoblast model. TG increased CYLD expression and induced cell Pyroptosis, while TUDCA mitigated these effects. CYLD silencing reduced trophoblast Pyroptosis, whereas overexpression negated TUDCA's inhibitory impact.

Discussion: Our findings indicate that ERS-mediated trophoblast Pyroptosis via CYLD under inflammatory conditions sheds light on PTB mechanisms, providing a potential target for modulating labor onset.

Keywords

CYLD; Endoplasmic reticulum stress; Inflammation; Labor; Preterm birth; Pyroptosis.

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