Sexually dimorphic effects of gestational endocrine-disrupting chemicals on microRNA expression in the developing rat hypothalamus.
Sexually dimorphic effects of gestational endocrine-disrupting chemicals on microRNA expression in the developing rat hypothalamus.
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DOI：
10.1016/j.mce.2015.07.013
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发表时间：
2015-10-15
影响因子：
4.1
通讯作者：
Gore AC
中科院分区：
文献类型：
--
作者：
Topper VY;Walker DM;Gore AC
这项研究检查了下丘脑microRNA的发育变化和性二态性，以及妊娠期暴露于环境内分泌干扰物（EDCs）是否改变了它们的表达模式。妊娠大鼠母鼠在妊娠第16天和第18天接受溶剂、苯甲酸雌二醇或多氯联苯混合物处理。在出生后第15、30、45或90天对雄性和雌性后代实施安乐死，并在下丘脑的内侧视前核（MPN）和腹内侧核（VMN）中定量microRNA和mRNA靶标。MicroRNA在两个区域都显示出强大的发育变化，并且在MPN中具有性二态性，但在VMN中没有。重要的是，女性中的microRNA在P30时被EDCs上调，而在P90时在男性中下调。因此，下丘脑microRNAs对产前EDC治疗敏感，具有性别、发育年龄和脑区特异性。
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.