Benoit-Pilven Clara, Asteljoki Juho V, Leinonen Jaakko T, Karjalainen Juha, Daly Mark J, Tukiainen Taru
Institute for Molecular Medicine Finland FIMM, HiLIFE, University of Helsinki, Helsinki, Finland.
Minerva Foundation Institute for Medical Research, Helsinki, Finland; Department of Internal Medicine, University of Helsinki, Helsinki, Finland; Abdominal Center, Helsinki University Hospital, Helsinki, Finland.
Cell Genom. 2025 Jul 9;5(7):100890. doi: 10.1016/j.xgen.2025.100890. Epub 2025 May 26.
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.
为了详细阐述在几种与大脑相关的表型中已确立的男女差异的起源，我们评估了发育中和成人大脑中转录组性别偏差的模式。我们发现，产前大脑中存在大量的表达性别差异（sex-DEs），这是由激素和性染色体因素共同驱动的，并且发育中和成人大脑之间的性别效应具有相当的一致性，几乎没有仅在成人大脑中存在的性别差异。性别差异在与脑部疾病相关的基因中并未富集，这与这些基因的特征（例如约束）的系统性差异一致。然而，在整个生命周期中具有持续性别差异的基因在疾病基因共调控网络中过度富集，表明它们有可能介导大脑表型中的性别偏差。总之，我们的工作强调产前发育是建立大脑性别差异的关键时间点。
