Multi- and Transgenerational Consequences of Bisphenol A on Sexually Dimorphic Cell Populations in Mouse Brain
Multi- and Transgenerational Consequences of Bisphenol A on Sexually Dimorphic Cell Populations in Mouse Brain
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DOI：
10.1210/en.2016-1188
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发表时间：
2017-01-01
期刊：
影响因子：
4.8
通讯作者：
Rissman, Emilie F.
中科院分区：
文献类型：
--
作者：
Goldsby, Jessica A.;Wolstenholme, Jennifer T.;Rissman, Emilie F.
双酚A（BPA）是一种用于制造塑料的内分泌干扰化合物;它存在于食品罐，瓶子，热收据和许多其他日常用品的衬里中，并且在人类尿液和血液中可检测到。在发育过程中暴露于BPA会破坏某些大脑区域的性别分化。此外，BPA可以对基因表达和行为产生跨代影响。在这里，我们使用了一种饮食和繁殖方案，对行为产生跨代影响。C57 BL/6 J小鼠在妊娠期间食用对照或含BPA的饮食。我们研究了加压素（AVP）和雌激素受体α（ER α）的免疫反应性（IR）的性二态脑区从第一代（F1）的后代和跨代的影响BPA在第三代的后代。除了一个脑区外，在两代对照小鼠中均观察到预期的性别差异。在F1代小鼠中，饮食性别相互作用存在于外侧隔和后背内侧杏仁核中的AVP免疫反应。在这两个区域，BPA暴露降低了男性大脑的免疫反应性。饮食和性别之间的相互作用，雌激素受体α-IR在下丘脑腹内侧的BPA暴露的女性免疫反应性降低。有趣的是，BPA对前腹侧室周核和终纹床核中的ER α-ir具有跨代影响。我们的数据表明，BPA产生的免疫反应性差异ER α-IR代暴露于BPA后。我们推测，BPA在子宫内对大脑中ER α-ir的作用对生殖和社会行为具有长期影响。
Bisphenol A (BPA) is an endocrine-disrupting compound used to manufacture plastics; it is present in linings of food cans, bottles, thermal receipts, and many other everyday items and is detectable in human urine and blood. Exposure to BPA during development can disrupt sexual differentiation of some brain regions. Moreover, BPA can have transgenerational effects on gene expression and behaviors. Here, we used a diet and breeding regimen that produces transgenerational effects on behaviors. C57BL/6J mice consumed control or BPA-containing diets during pregnancy. We examined vasopressin (AVP) and estrogen receptor alpha (ER alpha) immunoreactivity (ir) in sexually dimorphic brain regions from first-generation (F1) offspring and transgenerational effects of BPA in third-generation offspring. In all but one brain region examined, the expected sex differences were noted in both generations of control mice. In F1 mice, a diet by sex interaction was present for AVP-ir in the lateral septum and posterodorsal medial amygdala. In both regions, BPA exposure reduced immunoreactivity in male brains. An interaction between diet and sex for ER alpha-ir in the ventromedial hypothalamus was caused by reduced immunoreactivity in BPA-exposed females. Of interest, BPA had transgenerational effects on ER alpha-ir in the anteroventral periventricular nucleus and bed nucleus of the stria terminalis. Our data show that BPA produces immunoreactive differences in ER alpha-ir generations after exposure to BPA. We speculate that actions of BPA in utero on ER alpha-ir in brain have long-term consequences for reproduction and social behavior.