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Related Experiment Video

Updated: May 29, 2025

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Lactate promotes premature aging of preeclampsia placentas through histone lactylation-regulated GADD45A.

Xiang Li1, Qianghua Wang2, Jiaojiao Fei1

  • 1Anhui Province Key Laboratory of Clinical and Preclinical Research in Respiratory Disease, Molecular Diagnosis Center, The First Affiliated Hospital of Bengbu Medical University, Bengbu, 233004, Anhui, China.

Placenta
|February 5, 2025
PubMed
Summary
This summary is machine-generated.

Lactate accelerates placental aging in preeclampsia (PE) by promoting trophoblast cell senescence. This occurs via epigenetic upregulation of GADD45A, suggesting new therapeutic targets for PE.

Keywords:
GADD45AH3K18 lactylationLactatePreeclampsiaSenescence

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Area of Science:

  • Obstetrics and Gynecology
  • Cellular Biology
  • Epigenetics

Background:

  • Premature placental aging is associated with preeclampsia (PE).
  • Lactate is implicated in promoting cellular senescence.
  • This study investigates lactate's role in PE-related placental aging.

Purpose of the Study:

  • To explore the role of lactate in premature placental aging in preeclampsia.
  • To elucidate the underlying molecular mechanisms, focusing on cellular senescence and epigenetic modifications.

Main Methods:

  • Senescence markers were assessed using SA-β-Gal staining, western blotting, RT-qPCR, and immunofluorescence.
  • GADD45A expression was manipulated using siRNA in lactate-exposed trophoblast cells.
  • Histone lactylation at the GADD45A promoter was analyzed via ChIP-qPCR.

Main Results:

  • PE placentas showed increased senescence markers compared to controls.
  • Lactate exposure enhanced trophoblast senescence and P16 expression.
  • Lactate increased GADD45A expression and histone lactylation; GADD45A knockdown reduced lactate-induced senescence.

Conclusions:

  • Lactate drives trophoblast senescence through epigenetic upregulation of GADD45A.
  • This mechanism provides novel insights into PE pathogenesis.
  • Targeting lactate-induced epigenetic changes may offer new therapeutic strategies for PE.