Social and neuromolecular phenotypes are programmed by prenatal exposures to endocrine-disrupting chemicals.
Social and neuromolecular phenotypes are programmed by prenatal exposures to endocrine-disrupting chemicals.
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社会和神经分子表型是通过产前接触内分泌干扰化学物质来编程的。
DOI：
10.1016/j.mce.2018.09.010
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发表时间：
2019
影响因子：
4.1
通讯作者：
Gore,AndreaC
中科院分区：
文献类型：
--
作者：
Topper,ViktoriaY;Reilly,MichaelP;Wagner,LaurenM;Thompson,LindsayM;Gillette,Ross;Crews,David;Gore,AndreaC
暴露于内分泌干扰化学品（EDCs）会影响神经回路的发育，而神经回路的适当组织对于适当的成人社会和性行为的表现是必要的。我们研究了产前暴露于多氯联苯（PCBs），一个家庭的无处不在的工业污染物检测到几乎所有的人类和野生动物，引起的性二态社会互动和通信的变化，并描绘了潜在的神经分子表型。在胚胎第16和18天（E），用PCB商业混合物Aroclor 1221（A1221）、苯甲酸雌二醇（EB）（作为A1221雌激素效应的阳性对照）或溶剂（4% DMSO）处理大鼠。在成年F1后代中，我们首先进行了超声波发声（USV）的测试，在社会性的背景下，作为衡量动机的通信。某些USV呼叫类型的数量显着增加，产前治疗与A1221在男性中，和EB在女性中减少。在一个测试的社会性偏好的一个雌鼠与一个非激素引发的异性同种，男性（而不是女性）的鼻子触摸与异性大鼠显着减少内分泌干扰物。基因表达谱是在两个大脑区域进行的，这两个区域是大脑中社会决策网络的一部分：内侧视前核（MPN）和腹内侧核（VMN）。在这两个地区，更多的基因受到影响的A1221或EB在女性比男性。在雌性MPN中，A1221改变了类固醇激素受体和神经肽基因的表达（例如，Ar、Esr 1、Esr 2和Kiss 1）。在雄性MPN中，只有Per 2受A1221的影响。与溶剂相比，VMN中有许多基因受到EB的影响（雌性：Kiss 1、Kiss 1 r、Pgr;雄性：Crh），但不受A1221的影响。EB和A1221之间的这些差异表明A1221的作用机制超越了雌激素途径。这些数据表明，性别特异性的影响产前PCBs的成年人的行为和神经分子表型。
Exposures to endocrine-disrupting chemicals (EDCs) affect the development of hormone-sensitive neural circuits, the proper organization of which are necessary for the manifestation of appropriate adult social and sexual behaviors. We examined whether prenatal exposure to polychlorinated biphenyls (PCBs), a family of ubiquitous industrial contaminants detectable in virtually all humans and wildlife, caused changes in sexually-dimorphic social interactions and communications, and profiled the underlying neuromolecular phenotype. Rats were treated with a PCB commercial mixture, Aroclor 1221 (A1221), estradiol benzoate (EB) as a positive control for estrogenic effects of A1221, or the vehicle (4% DMSO), on embryonic day (E) 16 and 18. In adult F1 offspring, we first conducted tests of ultrasonic vocalization (USV) calls in a sociosexual context as a measure of motivated communications. Numbers of certain USV call types were significantly increased by prenatal treatment with A1221 in males, and decreased by EB in females. In a test of sociosexual preference for a hormone-vs. a non-hormone-primed opposite sex conspecific, male (but not female) nose-touching with opposite-sex rats was significantly diminished by EDCs. Gene expression profiling was conducted in two brain regions that are part of the social decision-making network in the brain: the medial preoptic nucleus (MPN) and the ventromedial nucleus (VMN). In both regions, many more genes were affected by A1221 or EB in females than males. In female MPN, A1221 changed expression of steroid hormone receptor and neuropeptide genes (e.g.,Ar, Esr1, Esr2,andKiss1). In male MPN, onlyPer2was affected by A1221. The VMN had a number of genes affected by EB compared to vehicle (females:Kiss1, Kiss1r, Pgr;males:Crh) but not A1221. These differences between EB and A1221 indicate that the mechanism of action of A1221 goes beyond estrogenic pathways. These data show sex-specific effects of prenatal PCBs on adult behaviors and the neuromolecular phenotype.