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Intermittent Propofol Exposure Induces Neurodevelopmental Alterations in Human Brain Organoids.

Sudena Wang1, Chloe Hall2, Yong Wang1,3

  • 1Department of Anesthesiology, University Medical Center, Johannes Gutenberg-University Mainz, Mainz, Germany.

Cellular and Molecular Neurobiology
|January 26, 2026
PubMed
Summary

Intermittent propofol exposure (IPE) during early pregnancy may accelerate fetal brain maturation. This study in human brain organoids (HBOs) suggests potential developmental deviations from anesthesia exposure.

Keywords:
AnestheticsHuman brain organoidsHuman cerebral organoidsNeurodevelopmentPropofol

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Area of Science:

  • Neuroscience
  • Developmental Biology
  • Toxicology

Background:

  • Anesthesia administration during pregnancy raises concerns for fetal brain development.
  • Human brain organoids (HBOs) offer a model to study these effects in vitro.

Purpose of the Study:

  • To investigate the impact of intermittent propofol exposure (IPE) on human brain organoid development.
  • To assess neurodevelopmental and synaptic gene expression changes following IPE.

Main Methods:

  • Human brain organoids (HBOs) derived from H1 embryonic stem cells were exposed to propofol (50 µM) at early (47-50 days in vitro) or late (77-80 days in vitro) developmental stages.
  • Organoids were analyzed at 60 or 90 days in vitro using multi-electrode array recordings and RNA-sequencing.
  • Neurotoxicity was assessed via growth and lactate release measurements.

Main Results:

  • Propofol exposure did not induce neurotoxicity in HBOs.
  • Early IPE led to increased neuronal activity at 60 days in vitro, an effect not seen with late IPE at 90 days in vitro.
  • IPE upregulated genes related to neurodevelopment and synapse function, coinciding with natural developmental gene expression patterns.

Conclusions:

  • Early intermittent propofol exposure may accelerate brain maturation in human brain organoids.
  • These findings suggest that prenatal anesthesia exposure could alter normal fetal brain developmental trajectories.