Genetic and epigenetic mechanisms of infertility caused by endocrine disrupting chemicals
内分泌干扰物引起不孕症的遗传和表观遗传机制
基本信息
- 批准号:10487840
- 负责人:
- 金额:$ 52.99万
- 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:2021-11-01 至 2024-10-31
- 项目状态:已结题
- 来源:
- 关键词:AdultAgonistAgricultureAryl Hydrocarbon ReceptorAwardBiological MarkersCellsCharacteristicsChemical ExposureChromatinClinicalCritical PathwaysDNA Modification MethylasesDataDefectDevelopmentDiseaseElderlyEndocrine DisruptorsEpidemicEpidemiologyEpigenetic ProcessExposure toFemaleFishesFood ChainFood SupplyGene ExpressionGenerationsGenesGeneticGenomeGenomicsGoalsHeritabilityHumanIncidenceIndustrializationInfertilityInvestigationKnowledgeLaboratoriesLeadLifeMale InfertilityMediatingMetabolicMetabolismMethylationMitochondriaModificationMolecularMutationNational Institute of Environmental Health SciencesOutcomePathway interactionsPharmacologic SubstancePhenotypePlayPollutionPopulationPredispositionPreventionProcessPublic HealthReproductive HealthReproductive systemResearchRisk AssessmentRoleSelf CareSentinelSeriesSpermatogenesisStructureTesticular TissueTestingTestisTetrachlorodibenzodioxinTherapeuticTimeTissuesToxic Environmental SubstancesToxicant exposureToxinTransgenic OrganismsZebrafishcell typediagnostic strategyepigenetic regulationepigenomeevidence basefightingglucose metabolismgonad developmentgrasphistone methyltransferasehistone modificationhuman maleinsightlipid metabolismmalepreventprototypereproductivereproductive system disorderresponsesingle cell sequencingsperm celltoxicanttranscriptomicstreatment strategy
项目摘要
PROJECT SUMMARY
A single toxicant exposure during development can produce reproductive defects in adulthood and subsequent
generations, presenting a major hurdle in the prevention and treatment of human infertility. Despite its
significance, however, the mechanisms that mediate this process are poorly understood. Endocrine disrupting
chemicals (EDCs) play a role in the increasing incidence of male infertility worldwide, and mounting evidence
suggests that EDC exposure can alter gene expression and the epigenome. Our long-term goal is to determine
how environmental toxicants interfere with reproductive health so that evidence-based strategies to prevent
and treat adult-onset and transgenerational disease can be developed.!The overall objective for this NIEHS
R01 Award (PA-19-056) application is to determine genome function alterations and epigenetic regulation of
environmentally-influenced infertility. The central hypothesis is that sublethal EDC exposure during male gonad
development leads to genomic and epigenetic dysregulation that alters testicular mitochondrial function in
exposed generation and subsequent generations. The rationale for the proposed research is that investigation
of the mechanisms underlying EDC induced infertility will advance prevention, risk-assessment, diagnostic,
and treatment strategies for human male infertility. Guided by strong preliminary data, this hypothesis will be
tested by pursuing three specific aims: 1) Determine testicular cell-type specific and life stage specific changes
in genome function to identify critical windows for biomarkers of effect and gene relationships; 2) Identify
changes in the epigenome related to phenotypic and genetic endpoints; 3) Determine multigenerational and
transgenerational cell-specific transcriptomic and epigenetic changes induced by ancestral exposure.
Ultimately, these results will identify critical windows for biomarkers of effect, inform the interplay among
pathways mediating toxic endpoints.
项目总结
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)
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Tracie R Baker其他文献
Tracie R Baker的其他文献
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{{ truncateString('Tracie R Baker', 18)}}的其他基金
Transcriptomic and epigenetic mechanisms of lead (Pb)-induced neurobehavioral disease in aged populations and subsequent generations
铅(Pb)诱导的老年人群及后代神经行为疾病的转录组和表观遗传机制
- 批准号:
10577926 - 财政年份:2023
- 资助金额:
$ 52.99万 - 项目类别:
Developmental VOC Exposure in Zebrafish: Toxic Mechanisms and Biomarkers
斑马鱼发育过程中 VOC 暴露:毒性机制和生物标志物
- 批准号:
10700804 - 财政年份:2022
- 资助金额:
$ 52.99万 - 项目类别:
Developmental VOC Exposure in Zebrafish: Toxic Mechanisms and Biomarkers
斑马鱼发育过程中 VOC 暴露:毒性机制和生物标志物
- 批准号:
10352964 - 财政年份:2022
- 资助金额:
$ 52.99万 - 项目类别:
Genetic and epigenetic mechanisms of infertility caused by endocrine disrupting chemicals
内分泌干扰物引起不孕症的遗传和表观遗传机制
- 批准号:
10516110 - 财政年份:2021
- 资助金额:
$ 52.99万 - 项目类别:
Genetic and epigenetic mechanisms of infertility caused by endocrine disrupting chemicals
内分泌干扰物引起不孕症的遗传和表观遗传机制
- 批准号:
9911309 - 财政年份:2019
- 资助金额:
$ 52.99万 - 项目类别:
Adult and Transgenerational Toxicity Due to Developmental TCDD Exposure
发育期接触 TCDD 导致的成人和跨代毒性
- 批准号:
8443233 - 财政年份:2013
- 资助金额:
$ 52.99万 - 项目类别:
Adult and Transgenerational Toxicity Due to Developmental TCDD Exposure
发育期接触 TCDD 导致的成人和跨代毒性
- 批准号:
8685364 - 财政年份:2013
- 资助金额:
$ 52.99万 - 项目类别:
Adult and Transgenerational Toxicity Due to Developmental TCDD Exposure
发育期接触 TCDD 导致的成人和跨代毒性
- 批准号:
8827435 - 财政年份:2013
- 资助金额:
$ 52.99万 - 项目类别:
Adult and Transgenerational Toxicity Due to Developmental TCDD Exposure
发育期接触 TCDD 导致的成人和跨代毒性
- 批准号:
9252687 - 财政年份:2013
- 资助金额:
$ 52.99万 - 项目类别:
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