Early establishment and life course stability of sex biases in the human brain transcriptome.

Cell genomics
Authors
Keywords
Abstract

To elaborate on the origins of the established male-female differences in several brain-related phenotypes, we assessed the patterns of transcriptomic sex biases in the developing and adult human forebrain. We find an abundance of sex differences in expression (sex-DEs) in the prenatal brain, driven by both hormonal and sex-chromosomal factors, and considerable consistency in the sex effects between the developing and adult brain, with little sex-DE exclusive to the adult forebrain. Sex-DE was not enriched in genes associated with brain disorders, consistent with systematic differences in the characteristics of these genes (e.g., constraint). Yet, the genes with persistent sex-DE across the lifespan were overrepresented in disease gene co-regulation networks, pointing to their potential to mediate sex biases in brain phenotypes. Altogether, our work highlights prenatal development as a crucial time point for the establishment of brain sex differences.

Year of Publication
2025
Journal
Cell genomics
Volume
5
Issue
7
Pages
100890
Date Published
07/2025
ISSN
2666-979X
DOI
10.1016/j.xgen.2025.100890
PubMed ID
40425010
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