Topper Viktoria Y, Walker Deena M, Gore Andrea C
Institute for Cellular and Molecular Biology, The University of Texas at Austin, Austin, TX 78712, USA.
Institute for Neuroscience, The University of Texas at Austin, Austin, TX 78712, USA.
Mol Cell Endocrinol. 2015 Oct 15;414:42-52. doi: 10.1016/j.mce.2015.07.013. Epub 2015 Jul 17.
This study examined developmental changes and sexual dimorphisms in hypothalamic microRNAs, and whether gestational exposures to environmental endocrine-disrupting chemicals (EDCs) altered their expression patterns. Pregnant rat dams were treated on gestational days 16 and 18 with vehicle, estradiol benzoate, or a mixture of polychlorinated biphenyls. Male and female offspring were euthanized on postnatal days (P) 15, 30, 45, or 90, and microRNA and mRNA targets were quantified in the medial preoptic nucleus (MPN) and ventromedial nucleus (VMN) of the hypothalamus. MicroRNAs showed robust developmental changes in both regions, and were sexually dimorphic in the MPN, but not VMN. Importantly, microRNAs in females were up-regulated by EDCs at P30, and down-regulated in males at P90. Few changes in mRNAs were found. Thus, hypothalamic microRNAs are sensitive to prenatal EDC treatment in a sex-, developmental age-, and brain region-specific manner.
本研究检测了下丘脑微小RNA的发育变化和性别差异，以及孕期暴露于环境内分泌干扰化学物（EDCs）是否会改变其表达模式。怀孕的大鼠母鼠在妊娠第16天和18天接受溶剂、苯甲酸雌二醇或多氯联苯混合物处理。雄性和雌性后代在出生后第（P）15、30、45或90天安乐死，下丘脑内侧视前核（MPN）和腹内侧核（VMN）中的微小RNA和mRNA靶点进行定量分析。微小RNA在两个区域均显示出显著的发育变化，且在MPN中存在性别差异，但在VMN中没有。重要的是，雌性中的微小RNA在P30时被EDCs上调，而在雄性中在P90时被下调。在mRNA中未发现明显变化。因此，下丘脑微小RNA对产前EDC处理具有性别、发育年龄和脑区特异性的敏感性。
