Humans display reproducible sex differences in cognition and behavior, which may partly reflect intrinsic sex differences in regional brain organization. However, the consistency, causes and consequences of sex differences in the human brain are poorly characterized and hotly debated. In contrast, recent studies in mice—a major model organism for studying neurobiological sex differences—have established: 1) highly consistent sex biases in regional gray matter volume (GMV) involving the cortex and classical subcortical foci, 2) a preponderance of regional GMV sex differences in brain circuits for social and reproductive behavior, and 3) a spatial coupling between regional GMV sex biases and brain expression of sex chromosome genes in adulthood. Here, we directly test translatability of rodent findings to humans. First, using two independent structural-neuroimaging datasets (n > 2,000), we find that the spatial map of sex-biased GMV in humans is highly reproducible (r > 0.8 within and across cohorts). Relative GMV is female biased in prefrontal and superior parietal cortices, and male biased in ventral occipitotemporal, and distributed subcortical regions. Second, through systematic comparison with functional neuroimaging meta-analyses, we establish a statistically significant concentration of human GMV sex differences within brain regions that subserve face processing. Finally, by imaging-transcriptomic analyses, we show that GMV sex differences in human adulthood are specifically and significantly coupled to regional expression of sex-chromosome (vs. autosomal) genes and enriched for distinct cell-type signatures. These findings establish conserved aspects of sex-biased brain development in humans and mice, and shed light on the consistency, candidate causes, and potential functional corollaries of sex-biased brain anatomy in humans.

人类在认知和行为上表现出可再现的性别差异，这可能部分反映了区域性大脑组织的内在性别差异。但是，人脑性别差异的一致性，原因和后果的特征不清，争论不休。相反，最近在小鼠中的研究-一种研究神经生物学性别差异的主要模型生物-已建立：1）涉及皮质和经典皮层下灶的区域灰质体积（GMV）高度一致的性别偏见，2）区域GMV占优势社交和生殖行为在大脑回路中的性别差异，以及3）成年后区域GMV性别偏见与性染色体基因的大脑表达之间存在空间耦合。在这里，我们直接测试啮齿动物发现对人类的可翻译性。第一，n > 2,000），我们发现人类性别偏向性GMV的空间图具有很高的再现性（r队列内和跨队列> 0.8）。相对GMV在前额皮层和上顶叶皮层中有女性偏爱，在腹侧枕颞叶和分布的皮层下区域偏爱男性。其次，通过与功能性神经影像荟萃分析的系统比较，我们建立了在人脸GMV性别差异上具有统计学意义的集中度，这些差异在为面部处理服务的大脑区域内。最后，通过成像转录组分析，我们表明人类成年时期的GMV性别差异与性染色体（相对于常染色体）基因的区域表达特别且显着相关，并富集了独特的细胞类型特征。这些发现建立了人类和小鼠性别偏向的大脑发育的保守方面，并阐明了一致性，候选原因，