ArticleBiology of sex differences2025
Sex-dimorphic reprogramming of fetal mouse brain development by maternal estradiol excess.
Article in Biology of sex differences, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
1 citing paper in PubMed.
- Before hormones: early sex-specific mechanisms shaping nervous system development, function, and postnatal disease susceptibility.Frontiers in behavioral neuroscience · 2026Review
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Authors and funding
6 authors.
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Abstract
backgroundGestational environmental perturbations can induce sex-specific developmental programming, increasing offspring susceptibility to chronic diseases. While prenatal high estradiol (HE) exposure has been associated with male-biased neurodevelopmental disorders, the underlying mechanisms remain poorly understood.
methodsUsing spatial transcriptomics in a murine HE exposure model, we systematically characterized sex-divergent molecular and cellular responses in fetal brains. Through cell type identification, spatial mapping, ligand-receptor interaction analysis, and transcription factor activity assessment, we examined gene expression profile, intra-regional signaling pathway, and regulon activity variations. Additionally, we performed immunofluorescence to characterize neural progenitor cell dynamics.
resultsOur analysis revealed that maternal HE exposure differentially altered gene expression patterns between male and female fetal brain regions, with more pronounced effects on male-biased genes. Notably, HE-induced downregulation of male-biased genes was proportional to their baseline male-bias degree. We uncovered region-specific cellular responses to HE exposure and demonstrated sex-opposed alterations in intra-regional signaling pathway. Furthermore, we identified cell type- and brain region-restricted sex differences in regulon activity variations. Histological validation confirmed that maternal HE exposure specifically disrupts the proliferation-differentiation balance of neural progenitor cells in the male cerebral cortex.
conclusionsThese findings provide mechanistic insights into sex-dimorphic developmental reprogramming of fetal brain by maternal estradiol excess. They establish a framework for developing targeted interventions against gestational endocrine disruption-induced neurodevelopmental disorders.
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