Effects of endocrine-disrupting chemicals on hypothalamic oxytocin and vasopressin systems.
Effects of endocrine-disrupting chemicals on hypothalamic oxytocin and vasopressin systems.
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DOI：
10.1002/jez.2475
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发表时间：
2022-01
期刊：
影响因子：
--
通讯作者：
Gore AC
中科院分区：
文献类型：
--
作者：
Reilly MP;Kunkel MN;Thompson LM;Zentay A;Weeks CD;Crews D;Cormack LK;Gore AC
暴露于内分泌干扰化学品（EDCs）会扰乱荷尔蒙系统。由于发育中的生物体对激素作用的高度敏感性，当暴露于胎儿和婴儿时，内分泌干扰物特别成问题。以前的研究表明，产前多氯联苯（PCB）暴露破坏下丘脑发育，生殖生理，择偶行为，和社会行为的性二态性的方式。基于证据表明，内分泌干扰物在啮齿动物的社会行为，我们研究了多氯联苯的神经肽催产素（OXT）和加压素（AVP）系统，参与调节这些行为的影响。将大鼠在产前（妊娠第16天和第18天）暴露于弱雌激素PCB混合物Aroclor 1221（0.5或1 mg/kg）、苯甲酸雌二醇（EB，阳性对照）或溶剂（3% DMSO）。在成年人（~P90）脑中，我们计数了下丘脑室旁核（PVN）和视上核（SON）中的催产素和加压素免疫标记细胞数。内分泌干扰物并没有改变绝对数量的催产素或加压素细胞在这两个地区，虽然有一些温和的变化，在吻尾分布。其次，通过qPCR测定这些九肽（Oxt、Avp）、其受体（Oxtr、Avpr 1a）和雌激素受体β（Esr 2）的基因表达。在PVN，有剂量依赖性的影响，多氯联苯在男性（Oxt，Oxtr），和EB的影响，在女性（Avp，Esr 2）。在SON中，雄性动物的Oxt和Esr 2受到给药的影响。产前治疗引起的蛋白质和基因表达的这些变化表明，转录和转录后机制在介导内分泌干扰物如何重编程下丘脑发育中发挥作用。出生前多氯联苯暴露对下丘脑室旁核和视上核内催产素神经元的分布有影响。显示的是相对于前囟从吻侧（左）到尾侧（右）的一系列免疫标记切片。
Exposures to endocrine disrupting chemicals (EDCs) perturb hormonal systems. EDCs are particularly problematic when exposure happens in the fetus and infant due to the high sensitivity of developing organisms to hormone actions. Previous work has shown that prenatal polychlorinated biphenyl (PCB) exposure disrupts hypothalamic development, reproductive physiology, mate preference behavior, and social behaviors in a sexually dimorphic manner. Based on evidence that EDCs perturb social behaviors in rodents, we examined effects of PCBs on the neuropeptides oxytocin (OXT) and vasopressin (AVP) systems that are involved in regulating these behaviors. Rats were exposed prenatally (gestational days 16 and 18) to the weakly estrogenic PCB mixture Aroclor 1221 (0.5 or 1 mg/kg), to estradiol benzoate (EB, a positive control), or to the vehicle (3% DMSO). In adult (~P90) brains, we counted immunolabeled oxytocin and vasopressin cell numbers in the paraventricular nucleus (PVN) and supraoptic nucleus (SON) of the hypothalamus. EDCs did not change absolute numbers of oxytocin or vasopressin cells in either region, although there were some modest shifts in the rostral-caudal distribution. Second, expression of genes for these nonapeptides (Oxt, Avp), their receptors (Oxtr, Avpr1a), and the estrogen receptor beta (Esr2), was determined by qPCR. In the PVN, there were dose-dependent effects of PCBs in males (Oxt, Oxtr), and effects of EB in females (Avp, Esr2). In the SON, Oxt and Esr2 were affected by treatments in males. These changes to protein and gene expression caused by prenatal treatments suggest that transcriptional and post-transcriptional mechanisms play roles in mediating how EDCs reprogram hypothalamic development. The distribution of oxytocin neurons in the PVN and SON was affected by prenatal PCB exposure. Shown is a series of immunolabeled sections from rostral (left) to caudal (right), relative to Bregma.
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影响因子：
10.4
作者：
Braun JM;Kalkbrenner AE;Just AC;Yolton K;Calafat AM;Sjödin A;Hauser R;Webster GM;Chen A;Lanphear BP
通讯作者：
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3.4
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16.2
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影响因子：
2.9
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通讯作者：
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