Mouse Imaging Centre and Program in Neuroscience and Mental Health, The Hospital for Sick Children, 25 Orde Street, Toronto, ON, M5T 3H7, Canada; Department of Medical Biophysics, The University of Toronto, 101 College Street, Suite 15-701, Toronto, ON, M5G 1L7, Canada.
Division of Endocrinology, The Hospital for Sick Children, 555 University Avenue, Toronto, ON, M5G 1X8, Canada.
Neuroimage. 2018 Jun;173:551-563. doi: 10.1016/j.neuroimage.2018.02.051. Epub 2018 Mar 2.
Biological sex influences brain anatomy across many species. Sex differences in brain anatomy have classically been attributed to differences in sex chromosome complement (XX versus XY) and/or in levels of gonadal sex steroids released from ovaries and testes. Using the four core genotype (4CG) mouse model in which gonadal sex and sex chromosome complement are decoupled, we previously found that sex hormones and chromosomes influence the volume of distinct brain regions. However, recent studies suggest there may be more complex interactions between hormones and chromosomes, and that circulating steroids can compensate for and/or mask underlying chromosomal effects. Moreover, the impact of pre vs post-pubertal sex hormone exposure on this sex hormone/sex chromosome interplay is not well understood. Thus, we used whole brain high-resolution ex-vivo MRI of intact and pre-pubertally gonadectomized 4CG mice to investigate two questions: 1) Do circulating steroids mask sex differences in brain anatomy driven by sex chromosome complement? And 2) What is the contribution of pre- versus post-pubertal hormones to sex-hormone-dependent differences in brain anatomy? We found evidence of both cooperative and compensatory interactions between sex chromosomes and sex hormones in several brain regions, but the interaction effects were of low magnitude. Additionally, most brain regions affected by sex hormones were sensitive to both pre- and post-pubertal hormones. This data provides further insight into the biological origins of sex differences in brain anatomy.
生物性别会影响许多物种的大脑解剖结构。大脑解剖结构的性别差异传统上归因于性染色体组成（XX 对 XY）和/或卵巢和睾丸释放的性腺性激素水平的差异。我们之前使用性腺性别和性染色体组成分离的四个核心基因型（4CG）小鼠模型发现，性激素和染色体会影响不同脑区的体积。然而，最近的研究表明，激素和染色体之间可能存在更复杂的相互作用，循环类固醇可以补偿和/或掩盖潜在的染色体效应。此外，青春期前和青春期后性激素暴露对这种性激素/性染色体相互作用的影响尚不清楚。因此，我们使用完整和青春期前性腺切除术的 4CG 小鼠的全脑高分辨率离体 MRI 来研究两个问题：1）循环类固醇是否掩盖了性染色体组成驱动的大脑解剖结构的性别差异？2） 青春期前和青春期后激素对性激素依赖性大脑解剖差异的贡献是什么？我们在几个大脑区域发现了性染色体和性激素之间存在合作和补偿相互作用的证据，但相互作用的影响程度较小。此外，受性激素影响的大多数大脑区域对青春期前和青春期后的激素都敏感。该数据进一步深入了解了大脑解剖结构性别差异的生物学起源。
