Department of Medical Genetics, University of British Columbia | BC Children's Hospital Research Institute, 938 W 28th Ave, Vancouver, BC, V5Z 4H4, Canada.
Department of Psychology and Human Development, Vanderbilt University, 230 Appleton Pl, Nashville, TN, 37203, USA.
BMC Genomics. 2020 Jun 3;21(1):389. doi: 10.1186/s12864-020-06789-3.
There are significant sex differences in human physiology and disease; the genomic sources of these differences, however, are not well understood. During puberty, a drastic neuroendocrine shift signals physical changes resulting in robust sex differences in human physiology. Here, we explore how shifting patterns of DNA methylation may inform these pathways of biological plasticity during the pubertal transition. In this study we analyzed DNA methylation (DNAm) in saliva at two time points across the pubertal transition within the same individuals. Our purpose was to compare two domains of DNAm patterns that may inform processes of sexual differentiation 1) sex related sites, which demonstrated differences between males from females and 2) time related sites in which DNAm shifted significantly between timepoints. We further explored the correlated network structure sex and time related DNAm networks and linked these patterns to pubertal stage, assays of salivary testosterone, a reliable diagnostic of free, unbound hormone that is available to act on target tissues, and overlap with androgen response elements.
Sites that differed by biological sex were largely independent of sites that underwent change across puberty. Time-related DNAm sites, but not sex-related sites, formed correlated networks that were associated with pubertal stage. Both time and sex DNAm networks reflected salivary testosterone levels that were enriched for androgen response elements, with sex-related DNAm networks being informative of testosterone levels above and beyond biological sex later in the pubertal transition.
These results inform our understanding of the distinction between sex- and time-related differences in DNAm during the critical period of puberty and highlight a novel linkage between correlated patterns of sex-related DNAm and levels of salivary testosterone.
人类生理学和疾病存在显著的性别差异；然而，这些差异的基因组来源尚不清楚。在青春期，剧烈的神经内分泌转变标志着身体发生变化，导致人类生理学出现显著的性别差异。在这里，我们探讨了 DNA 甲基化（DNAm）的变化模式如何为青春期过渡期间的这些生物学可塑性途径提供信息。在这项研究中，我们在个体的青春期过渡期间的两个时间点分析了唾液中的 DNA 甲基化（DNAm）。我们的目的是比较两种可能为性分化过程提供信息的 DNAm 模式区域：1）性别相关位点，这些位点显示男性和女性之间的差异；2）时间相关位点，其中 DNAm 在两个时间点之间发生了显著变化。我们进一步探索了相关的网络结构：性别和时间相关的 DNAm 网络，并将这些模式与青春期阶段、唾液睾酮检测结果相关联，睾酮是一种可靠的游离、未结合激素诊断试剂，可作用于靶组织，并与雄激素反应元件重叠。
性别差异的位点在很大程度上独立于跨越青春期发生变化的位点。时间相关的 DNAm 位点，而不是性别相关的位点，形成了与青春期阶段相关的相关网络。时间和性别 DNAm 网络都反映了唾液睾酮水平，这些水平富含雄激素反应元件，性别相关的 DNAm 网络在青春期过渡后期，除了生物学性别外，还能提供关于睾酮水平的信息。
这些结果为我们理解青春期这一关键时期 DNAm 中性别和时间相关差异提供了信息，并强调了相关的性别相关 DNAm 模式与唾液睾酮水平之间的新联系。
