Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Toxicol Appl Pharmacol. 2011 Oct 15;256(2):179-90. doi: 10.1016/j.taap.2011.08.008. Epub 2011 Aug 12.
The influence of sex as an effect modifier of childhood lead poisoning has received little systematic attention. Considering the paucity of information available concerning the interactive effects of lead and sex on the brain, the current study examined the interactive effects of lead and sex on gene expression patterns in the hippocampus, a structure involved in learning and memory. Male or female rats were fed either 1500 ppm lead-containing chow or control chow for 30 days beginning at weaning.Blood lead levels were 26.7±2.1 μg/dl and 27.1±1.7 μg/dl for females and males, respectively. The expression of 175 unique genes was differentially regulated between control male and female rats. A total of 167 unique genes were differentially expressed in response to lead in either males or females. Lead exposure had a significant effect without a significant difference between male and female responses in 77 of these genes. In another set of 71 genes, there were significant differences in male vs. female response. A third set of 30 genes was differentially expressed in opposite directions in males vs. females, with the majority of genes expressed at a lower level in females than in males. Highly differentially expressed genes in males and females following lead exposure were associated with diverse biological pathways and functions. These results show that a brief exposure to lead produced significant changes in expression of a variety of genes in the hippocampus and that the response of the brain to a given lead exposure may vary depending on sex.
性别作为儿童铅中毒的效应修饰因子的影响很少受到系统关注。考虑到关于铅和性别对大脑的相互作用影响的信息很少，目前的研究检查了铅和性别对海马体基因表达模式的相互作用影响，海马体是一个与学习和记忆有关的结构。雄性或雌性大鼠从断奶开始，分别喂食 1500ppm 含铅的饲料或对照饲料 30 天。女性和男性的血液铅水平分别为 26.7±2.1μg/dl 和 27.1±1.7μg/dl。在雄性和雌性对照大鼠之间，有 175 个独特基因的表达存在差异调节。在雄性或雌性中，共有 167 个独特基因对铅有反应而表达不同。在这些基因中，有 77 个基因的铅暴露有显著影响，但雄性和雌性之间的反应没有显著差异。在另一组 71 个基因中，雄性与雌性之间的反应存在显著差异。第三组 30 个基因在雄性与雌性之间表达方向相反，大多数基因在雌性中的表达水平低于雄性。在雄性和雌性中，铅暴露后高度差异表达的基因与多种生物学途径和功能相关。这些结果表明，短暂暴露于铅会导致海马体中多种基因的表达发生显著变化，并且大脑对特定铅暴露的反应可能因性别而异。
