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Using Organoids to Model Sex Differences in the Human Brain.

Adam Pavlinek1,2, Dwaipayan Adhya3,4, Alex Tsompanidis3

  • 1Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.

Biological Psychiatry Global Open Science
|August 2, 2024
PubMed
Summary
This summary is machine-generated.

Sex differences in brain development are influenced by sex steroids and chromosomes. Human brain organoids offer a model to study these prenatal differences, though challenges remain.

Keywords:
AutismBrain organoidsSex chromosomesSex differencesSteroidsX chromosome inactivation

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Area of Science:

  • Neuroscience
  • Developmental Biology
  • Genetics

Background:

  • Sex differences in brain development are evident from prenatal stages, impacting conditions like autism.
  • Males typically exhibit larger brain volumes, with notable differences in the hippocampus and amygdala.
  • Sex steroids and sex chromosomes are key drivers of these developmental disparities.

Purpose of the Study:

  • To review the contributions of sex steroids and sex chromosomes to brain development.
  • To examine the role of X chromosome inactivation in sex differences.
  • To discuss the utility and limitations of human brain organoids for studying these phenomena.

Main Methods:

  • Review of existing literature on sex differences in neurodevelopment.
  • Analysis of studies utilizing human induced pluripotent stem cell-derived brain organoids.
  • Examination of genetic and hormonal influences on prenatal brain development.

Main Results:

  • Brain organoids reveal prenatal differences in cell proliferation and neuronal development.
  • Androgens are linked to increased neurogenesis of excitatory neurons.
  • X chromosome inactivation is a significant factor contributing to sex differences.

Conclusions:

  • Human brain organoids are a valuable tool for modeling complex genetic traits in prenatal brain development.
  • Further research is needed to address challenges in modeling X chromosome inactivation and organoid limitations.
  • Understanding sex differences in brain development is crucial for addressing neuropsychiatric conditions.