Neuroscience Training Program and Psychology Department, 1202 West Johnson Street, University of Wisconsin-Madison, Madison, WI 53706, USA.
Brain Behav Immun. 2011 Oct;25(7):1299-304. doi: 10.1016/j.bbi.2011.02.009. Epub 2011 Feb 23.
Variations in maternal care alter the developmental programming of some genes by creating lasting differences in DNA methylation patterns, such as the estrogen receptor alpha (ERα) promoter region. Interestingly, mother rats preferentially lick and groom their male offspring more than females; therefore, we questioned whether the somatosensory stimuli associated with maternal grooming influences potential sex differences in DNA methylation patterns within the developing amygdala, an area important for socioemotional processing. We report a sex difference in the DNA methylation pattern of specific CpG sites of the ERα promoter region within the developing amygdala. Specifically, males have higher levels of ERα promoter methylation contrasted to females. Increasing the levels of maternal stimuli in females masculinized ERα promoter methylation patterns to male-like levels. As expected, higher levels of ERα promoter methylation were associated with lower ERα mRNA levels. These data provide further evidence that the early neonatal environment, particularly maternal care, contributes to sex differences and early programming of the neonatal brain via an epigenetic mechanism.
母体照顾的变化通过在 DNA 甲基化模式上产生持久的差异来改变某些基因的发育编程，例如雌激素受体 alpha（ERα）启动子区域。有趣的是，母鼠更喜欢舔舐和梳理它们的雄性后代而不是雌性后代；因此，我们想知道与母体梳理相关的躯体感觉刺激是否会影响发育中的杏仁核内潜在的性别差异的 DNA 甲基化模式，杏仁核是一个对社会情感处理很重要的区域。我们报告了在发育中的杏仁核中 ERα 启动子区域的特定 CpG 位点的 DNA 甲基化模式存在性别差异。具体来说，雄性的 ERα 启动子甲基化水平与雌性相比更高。增加雌性的母体刺激水平会使 ERα 启动子甲基化模式向雄性化转变。正如预期的那样，ERα 启动子甲基化水平越高，ERα mRNA 水平越低。这些数据进一步证明，早期的新生儿环境，特别是母体照顾，通过表观遗传机制促进了性别差异和新生儿大脑的早期编程。
