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Interaction of BPA and soy isoflavones on sociosexual behavior

BPA 和大豆异黄酮对社会性行为的相互作用

基本信息

批准号：
8467718
负责人：
Heather B Patisaul
金额：
$ 21.53万
依托单位：
NORTH CAROLINA STATE UNIVERSITY RALEIGH
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-05-08 至 2015-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8467718
关键词：
Adolescence Adolescent Adoption Adult Adverse effects Age Amygdaloid structure Animals Anti-Anxiety Agents Anxiety Behavior Behavior assessment Behavioral Behavioral Assay Behavioral Mechanisms Brain Brain region Candidate Disease Gene Chemicals Child Consumption DNA Methylation Data Development Diet Disease Dopamine Receptor Elements Endocrine Disruptors Epidemiology Epigenetic Process Estrogens Exposure to Future Gene Expression Generalized Anxiety Disorder Genes Genistein Glucocorticoid Receptor Goals Human Hyperactive behavior Hypothalamic structure Incidence Individual Infant formula Intake Isoflavones Laboratories Lead Life Link Longevity Medial Mediating Mental disorders Methylation Molecular Molecular Profiling Moods Motor Activity Mouse Strains Mus Neurosecretory Systems Pathway interactions Pattern Perinatal Perinatal Exposure Phenotype Pregnancy Preoptic Areas Prevalence Primates Property Puberty Publishing Rattus Research Reverse Transcriptase Polymerase Chain Reaction Rodent Sex Behavior Structure of terminal stria nuclei of preoptic region Testing Weaning Wistar Rats Work bisphenol A bisulfite critical developmental period density girls mRNA Expression neurobehavioral nonhuman primate novel prenatal pup relating to nervous system research study sex soy soy protein isolate steroid hormone receptor

项目摘要

DESCRIPTION (provided by applicant): Prior work from this lab and others has revealed that perinatal exposure to bisphenol A (BPA) alters sociosexual and mood-related behaviors in rodents, primates, and humans in ways which are age and sex specific. These data suggest that developmental exposure to BPA and other endocrine disrupting compounds (EDCs) might be contributing to the growing prevalence of anxiety- and mood-related disorders in children and adults. Preliminary data from this laboratory reveal that many of these adverse behavioral effects do not manifest in Wistar rats maintained on a soy-rich diet, suggesting that soy isoflavones, such as genistein (GEN) have potentially counteracting effects. What remains to be determined, and will be the focus of the proposed work, is (1) if adoption of a soy-rich diet, either simultaneously or after BPA exposure can mitigate the adverse behavioral effects across the lifespan (2) if the individual isoflavone genistein (GEN) alone is sufficient to induce the counteracting effects and (3) if soy itself (in the absence of BPA) can induce behavioral changes. The latter is critical given the growing prevalence of soy infant formula. Thus, the experiments proposed herein will test the hypothesis that isoflavone consumption, even after BPA exposure has occurred, may help "undo" the deleterious behavioral effects of BPA. It is further hypothesized that BPA is not acting as an estrogen mimic, but rather, via an epigenetic mechanism. To test these possibilities animals will undergo behavioral assessment in juvenile and adult life and a high throughput approach will be used to identify both neural and transcriptional changes within key hypothalamic regions (amygdala, bed nucleus of the stria terminalis and medial preoptic area) accompanying the effects. The proposed studies have the potential to uncover novel mechanisms of BPA action within neurobehavioral pathways, including those not directly mediated by ERs, and how they might be mitigated by soy isoflavones such as GEN. Specific Aim 1 seeks to determine the degree to which consumption of a soy-rich diet or GEN can mitigate the sociosexual effects of developmental BPA exposure. Specific Aim 2 will explore the molecular mechanisms by which soy intake counters BPA effects by assessing the hypothalamic gene expression and DNA methylation changes that correlate with observed behavioral changes in juvenile and adult life.

描述(由申请人提供)：该实验室和其他实验室先前的工作表明，围产期暴露于双酚A(BPA)会改变啮齿动物、灵长类动物和人类的社会性行为和情绪相关行为，其方式具有年龄和性别特异性。这些数据表明，发育过程中暴露于双酚A和其他内分泌干扰物(EDCs)可能是导致儿童和成人焦虑和情绪相关障碍日益流行的原因之一。来自该实验室的初步数据显示，这些不良行为影响中的许多在坚持大豆丰富的饮食的Wistar大鼠中并不明显，这表明大豆异黄酮类，如染料木素(Genistein，Gen)具有潜在的抵消作用。有待确定的，也将是拟议工作的重点是：(1)同时或在双酚A暴露后采用富含大豆的饮食是否可以减轻一生中的不良行为影响；(2)如果单独的异黄酮染料木素(Genistein，GEN)足以诱导抵消作用；(3)大豆本身(在没有双酚A的情况下)是否可以诱导行为变化。鉴于大豆婴儿配方奶粉的日益流行，后者至关重要。因此，这里提出的实验将检验这一假设，即即使在双酚A暴露之后，摄入异黄酮也可能有助于“消除”双酚A的有害行为影响。进一步假设双酚A不是作为雌激素的模拟物，而是通过表观遗传机制发挥作用。为了测试这些可能性，动物将在青少年和成年生活中接受行为评估，并将使用高通量方法来识别伴随这些影响的关键下丘脑区域(杏仁核、终纹床核和内侧视前区)的神经和转录变化。这项拟议的研究有可能揭示BPA在神经行为通路中的新作用机制，包括那些不是由ER直接介导的机制，以及它们如何被大豆异黄酮(如Gen)缓解。具体目标1试图确定食用富含大豆的饮食或基因在多大程度上可以减轻发育中双酚A暴露的社会性影响。具体目标2将通过评估与观察到的青少年和成年生活中的行为变化相关的下丘脑基因表达和DNA甲基化变化，来探索大豆摄入对抗双酚A影响的分子机制。

项目成果

期刊论文数量（6）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Assessment of sex specific endocrine disrupting effects in the prenatal and pre-pubertal rodent brain.

DOI：
10.1016/j.jsbmb.2015.08.021
发表时间：
2016-06
期刊：
The Journal of steroid biochemistry and molecular biology
影响因子：
0
作者：
Rebuli ME;Patisaul HB
通讯作者：
Patisaul HB

A novel model for neuroendocrine toxicology: neurobehavioral effects of BPA exposure in a prosocial species, the prairie vole (Microtus ochrogaster).

神经内分泌毒理学的新模型：亲社会物种草原田鼠（田鼠）接触 BPA 的神经行为影响。

DOI：
10.1210/en.2014-1379
发表时间：
2014
期刊：
Endocrinology
影响因子：
4.8
作者：
Sullivan,AlanaW;Beach,ElsworthC;Stetzik,LucasA;Perry,Amy;D'Addezio,AlyssaS;Cushing,BruceS;Patisaul,HeatherB
通讯作者：
Patisaul,HeatherB

Soy but not bisphenol A (BPA) induces hallmarks of polycystic ovary syndrome (PCOS) and related metabolic co-morbidities in rats.