ORIGINAL RESEARCH article
Front. Cell. Neurosci.
Sec. Cellular Neuropathology
This article is part of the Research TopicInterneurons in pathological conditionsView all 5 articles
Neurosteroid withdrawal disrupts GABAergic system development in human cortical organoids: implications for preterm birth
Provisionally accepted
- 1Division of Neonatology, Department of Pediatrics, Columbia University, Vagelos College of Physicians and Surgeons and New York-Presbyterian Morgan Stanley Children’s Hospital, New York, NY 10032, USA, New York, United States
- 2Columbia Stem Cell Initiative, Stem Cell Core, Columbia University Irving Medical Center., New York, United States
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Preterm birth substantially elevates the risk of neurological and cognitive disorders. Recent evidence suggests that the abrupt loss of placental support, particularly the cessation of neurotrophic and neuroprotective hormones, alters neurodevelopmental trajectories and may contribute to neurodevelopmental risk associated with prematurity. Our study investigates how the placental steroid hormone, allopregnanolone (ALLO), affects cerebral cortex development using human cortical organoid models. Our findings reveal that while ALLO exposure produces modest effects on overall cortical development, its withdrawal specifically disrupts GABAergic but not glutamatergic neuronal development. These results demonstrate that placental hormones, including ALLO, may target specific neuronal populations critical for cortical function, identifying potential therapeutic interventions following placental loss in human preterm neonates.
Keywords: Organoids, Cerebral Cortex, Placenta, Brain Development, neurosteroid, Allopregnanolone, hormone, GABA
Received: 29 Sep 2025; Accepted: 18 Nov 2025.
Copyright: © 2025 Lacaille, Lebayle, Corneo, Vacher and Penn. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Anna A Penn, aap2216@cumc.columbia.edu
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