Assessing the effects of exposures to phthalates in both the female and male germlines
评估邻苯二甲酸盐暴露对雌性和雄性种系的影响
基本信息
- 批准号:10378497
- 负责人:
- 金额:$ 3.45万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-06-01 至 2024-05-31
- 项目状态:已结题
- 来源:
- 关键词:AddressAffectApoptosisCaenorhabditis elegansChemical ExposureChemical-Induced ChangeChemicalsChromatinChromosome PairingChromosomesComplexCongenital AbnormalityDataDefectDibutyl PhthalateDoseEndocrine DisruptorsEnvironmentEpidemiologyEventExposure toFemaleFetal DevelopmentFollow-Up StudiesGene ExpressionGenerationsGenetic NondisjunctionGerm CellsGoalsHealthHumanIllinoisImpairmentIncidenceIndividualInfertilityLaboratoriesLeadLightLinkMammalsMedicalMeiosisMethodologyMethodsModelingMorphogenesisMorphologyMusOogenesisOrganismPhthalic AcidsPhysiological ProcessesPlasticizersPredictive Value of TestsPregnant WomenProphaseRapid screeningReproductive HealthRiskRisk AssessmentSamplingShapesSpontaneous abortionTestingTimeToxic Environmental SubstancesToxinUnited States National Institutes of HealthUniversitiesUrineWorkbisphenol Acombinatorialdesigndiethylphthalateefficacy testingexposed human populationhigh throughput screeninginsightmalemouse modelphthalatesprognostic valueprogramsrepairedreproductive toxicityresponsescreeningstillbirth
项目摘要
Epidemiological and experimental data suggest that exposure to endocrine disrupting chemicals (EDCs) are linked to reproductive health issues including infertility, miscarriages, stillbirths, birth defects, and altered fetal development. Interestingly, some effects induced by EDC exposure have been shown to impact generations that extend beyond directly exposed individuals, suggesting that environmental toxins have transgenerational effects. Despite these indications, few studies have focused on the direct effects of EDCs on the germline. Furthermore, while humans are exposed to constant and variable mixtures of EDCs, most EDC studies have focused solely on the effects of single chemicals. Thus, understanding the additive, synergistic, and antagonistic effects between and among these chemicals is critical to understanding the risks they pose to human health. Because this is a daunting task in humans, I will combine studies in C. elegans and mice to test the efficacy of rapid screening in worms as a method of establishing relationships among common contaminants and assessing effects of chemical mixtures on the germline. My studies will focus specifically on a well characterized class of EDCs, namely phthalates, which are alkyl diesters of phthalic acid and widely used plasticizers found in various consumer, medical, and building products. Using six specific phthalates recently identified in human maternal urine, our preliminary studies found that individual exposure to BBP, DBP, DEP, DiBP, DiNP, and DEHP significantly increases chromosome nondisjunction and germ cell apoptosis during oogenesis in C. elegans. In this proposal, I aim to further characterize the individual effects of two of these phthalates (BBP and DEP) on chromosome morphogenesis, meiotic progression, germline-specific gene expression, and the chromatin landscape in both the female and male germlines. Lastly, I aim to determine the effects of all six phthalates in combination, as they exist in our environment, and assess how these effects are conserved across species. These proposed studies will not only shed light on the individual and combinatorial effects of these phthalates on both the female and male germlines, but the efficacy of using C. elegans to rapidly assess and predict the effects of environmental toxins on higher order organisms.
流行病学和实验数据表明,暴露于内分泌干扰物(EDCs)与生殖健康问题有关,包括不孕、流产、死产、出生缺陷和胎儿发育改变。有趣的是,EDC暴露引起的一些影响已经被证明影响到超过直接暴露的个人的世代,这表明环境毒素具有跨代影响。尽管有这些迹象,但很少有研究关注EDCs对生殖系的直接影响。此外,尽管人类暴露在恒定和可变的EDCs混合物中,但大多数EDC研究仅专注于单一化学品的影响。因此,了解这些化学品之间的相加、协同和拮抗效应对于了解它们对人类健康构成的风险至关重要。由于这在人类身上是一项艰巨的任务,我将结合对线虫和小鼠的研究,测试在蠕虫中进行快速筛查的有效性,以此作为建立常见污染物之间的关系和评估化学混合物对生殖系影响的一种方法。我的研究将特别集中在一类具有良好特性的EDCs上,即邻苯二甲酸酯,它是邻苯二甲酸的烷基双酯,在各种消费品、医疗和建筑产品中广泛使用的增塑剂。利用最近在人类母体尿液中发现的六种特定邻苯二甲酸酯,我们的初步研究发现,在线虫卵子发生过程中,单独暴露于BBP、DBP、DEP、DIBP、DNP和DEHP显著增加了染色体不分离和生殖细胞凋亡。在这项建议中,我的目标是进一步表征两种邻苯二甲酸酯(BBP和DEP)对染色体形态发生、减数分裂进程、生殖系特异性基因表达以及雌性和雄性生殖系中染色质景观的单独影响。最后,我的目标是确定所有六种邻苯二甲酸酯的组合的影响,因为它们存在于我们的环境中,并评估这些影响是如何在不同物种之间保存的。这些拟议的研究不仅将阐明这些邻苯二甲酸酯对雌性和雄性生殖系的个体和组合影响,而且还将阐明利用线虫快速评估和预测环境毒素对高级生物的影响的有效性。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Ayana Henderson其他文献
Ayana Henderson的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Ayana Henderson', 18)}}的其他基金
Assessing the effects of exposures to phthalates in both the female and male germlines
评估邻苯二甲酸盐暴露对雌性和雄性种系的影响
- 批准号:
10626868 - 财政年份:2021
- 资助金额:
$ 3.45万 - 项目类别:
相似海外基金
How Does Particle Material Properties Insoluble and Partially Soluble Affect Sensory Perception Of Fat based Products
不溶性和部分可溶的颗粒材料特性如何影响脂肪基产品的感官知觉
- 批准号:
BB/Z514391/1 - 财政年份:2024
- 资助金额:
$ 3.45万 - 项目类别:
Training Grant
BRC-BIO: Establishing Astrangia poculata as a study system to understand how multi-partner symbiotic interactions affect pathogen response in cnidarians
BRC-BIO:建立 Astrangia poculata 作为研究系统,以了解多伙伴共生相互作用如何影响刺胞动物的病原体反应
- 批准号:
2312555 - 财政年份:2024
- 资助金额:
$ 3.45万 - 项目类别:
Standard Grant
RII Track-4:NSF: From the Ground Up to the Air Above Coastal Dunes: How Groundwater and Evaporation Affect the Mechanism of Wind Erosion
RII Track-4:NSF:从地面到沿海沙丘上方的空气:地下水和蒸发如何影响风蚀机制
- 批准号:
2327346 - 财政年份:2024
- 资助金额:
$ 3.45万 - 项目类别:
Standard Grant
Graduating in Austerity: Do Welfare Cuts Affect the Career Path of University Students?
紧缩毕业:福利削减会影响大学生的职业道路吗?
- 批准号:
ES/Z502595/1 - 财政年份:2024
- 资助金额:
$ 3.45万 - 项目类别:
Fellowship
感性個人差指標 Affect-X の構築とビスポークAIサービスの基盤確立
建立个人敏感度指数 Affect-X 并为定制人工智能服务奠定基础
- 批准号:
23K24936 - 财政年份:2024
- 资助金额:
$ 3.45万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Insecure lives and the policy disconnect: How multiple insecurities affect Levelling Up and what joined-up policy can do to help
不安全的生活和政策脱节:多种不安全因素如何影响升级以及联合政策可以提供哪些帮助
- 批准号:
ES/Z000149/1 - 财政年份:2024
- 资助金额:
$ 3.45万 - 项目类别:
Research Grant
How does metal binding affect the function of proteins targeted by a devastating pathogen of cereal crops?
金属结合如何影响谷类作物毁灭性病原体靶向的蛋白质的功能?
- 批准号:
2901648 - 财政年份:2024
- 资助金额:
$ 3.45万 - 项目类别:
Studentship
Investigating how double-negative T cells affect anti-leukemic and GvHD-inducing activities of conventional T cells
研究双阴性 T 细胞如何影响传统 T 细胞的抗白血病和 GvHD 诱导活性
- 批准号:
488039 - 财政年份:2023
- 资助金额:
$ 3.45万 - 项目类别:
Operating Grants
New Tendencies of French Film Theory: Representation, Body, Affect
法国电影理论新动向:再现、身体、情感
- 批准号:
23K00129 - 财政年份:2023
- 资助金额:
$ 3.45万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
The Protruding Void: Mystical Affect in Samuel Beckett's Prose
突出的虚空:塞缪尔·贝克特散文中的神秘影响
- 批准号:
2883985 - 财政年份:2023
- 资助金额:
$ 3.45万 - 项目类别:
Studentship