Fetal Brain Development Establishes Lifelong Sex-Based Differences in Gene Activity

A comprehensive international study led by scientists at the Institute for Molecular Medicine Finland (FIMM), University of Helsinki, reveals that many of the molecular differences observed between male and female brains are established during the first trimester of pregnancy. These early programming differences persist throughout a person’s life, influencing brain function and possibly the susceptibility to certain neurological conditions. The research analyzed RNA sequencing data from 1,899 human forebrain samples, constructing a detailed timeline of sex-biased gene expression from early fetal development to old age.

Using publicly available datasets, the study examined prenatal brain samples collected between five and 17 weeks post-conception, alongside adult brain samples from individuals aged 20 to 79 years. The analysis identified over 3,000 genes with activity levels that differ between male and female fetal brains, compared to about 1,000 such genes in adults. Crucially, about two-thirds of these differences are specific to early development, with less than 1% appearing solely in adulthood. The remaining differences are present across both stages but tend to be smaller in adults.

Further investigation highlighted that prenatal sex differences are enriched for binding sites of androgen and estrogen receptors, underscoring the influence of early hormonal signals in establishing sex-specific brain features. "Our results demonstrate that sex differences in brain gene activity emerge remarkably early, long before birth, and many of these signatures remain into adulthood," explained Clara Benoit-Pilven, the first author of the study.

While these early expression differences are not directly linked to neurological diseases, they are overrepresented in gene networks associated with disorders such as schizophrenia and multiple sclerosis, suggesting a subtle influence on disease susceptibility. Additionally, the study found that X-chromosomal genes escaping X-inactivation show consistent female-biased expression across life, highlighting the stable role of sex chromosomes in brain development.

The researchers emphasize that understanding gene expression changes throughout development and aging is essential to unraveling the biological basis of phenotypic differences between sexes. These findings provide crucial insights into how early developmental processes shape lifelong brain function and health, offering new avenues for investigating sex-specific risks for neurological disorders.

Source: https://medicalxpress.com/news/2025-05-fetal-brain-wiring-life-sex.html