Psychology Department, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA.
Endocrinology. 2010 May;151(5):2297-305. doi: 10.1210/en.2009-0649. Epub 2010 Mar 17.
Sex differences in the brain are largely organized by a testicular hormone surge that occurs in males shortly after birth. Although this hormone surge is transient, sex differences in brain and behavior are lasting. Here we describe a sex difference in DNA methylation of the estrogen receptor-alpha (ERalpha) promoter region within the developing rat preoptic area, with males exhibiting more DNA methylation within the ERalpha promoter than females. More importantly, we report that simulating maternal grooming, a form of maternal interaction that is sexually dimorphic with males experiencing more than females during the neonatal period, effectively masculinizes female ERalpha promoter methylation and gene expression. This suggests natural variations in maternal care that are directed differentially at males vs. females can influence sex differences in the brain by creating sexually dimorphic DNA methylation patterns. We also find that the early estradiol exposure may contribute to sex differences in DNA methylation patterns. This suggests that early social interaction and estradiol exposure may converge at the genome to organize lasting sex differences in the brain via epigenetic differentiation.
大脑中的性别差异在很大程度上是由男性在出生后不久经历的睾丸激素激增组织的。尽管这种激素激增是短暂的，但大脑和行为的性别差异是持久的。在这里，我们描述了雄性大鼠前脑区发育过程中雌激素受体-α（ERα）启动子区域的 DNA 甲基化存在性别差异，雄性的 ERα 启动子中 DNA 甲基化程度高于雌性。更重要的是，我们报告说，模拟母体梳理，这是一种母体互动形式，在新生儿期雄性比雌性经历的更多，有效地使雌性 ERα 启动子甲基化和基因表达雄性化。这表明，针对男性和女性的自然差异的母婴护理会通过产生性别二态性的 DNA 甲基化模式来影响大脑中的性别差异。我们还发现，早期的雌二醇暴露可能导致 DNA 甲基化模式的性别差异。这表明，早期的社会互动和雌二醇暴露可能会在基因组上汇聚，通过表观遗传分化来组织大脑中持久的性别差异。
