Phthalate-Induced Ovulatory Dysfunction in Women
邻苯二甲酸盐引起的女性排卵功能障碍
基本信息
- 批准号:10241441
- 负责人:
- 金额:$ 24.9万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-09-02 至 2023-08-31
- 项目状态:已结题
- 来源:
- 关键词:AcademiaAcademic skillsAddressAgeAmphiregulinAnimal ModelAreaAwardBiological AssayCell modelCellsCosmeticsDataDefectDevelopment PlansEndocrineEndocrine DisruptorsEventExcipientsExposure toFemaleFemale infertilityFertilityFertility DisordersFunctional disorderGene ExpressionGene ProteinsGoalsGranulosa-Lutein CellsHealthHealthcareHumanHuman Chorionic GonadotropinImpairmentIn VitroInfertilityInterventionLeadLeukocytesLiteratureLuteinizing HormoneMeasurementMediatingMediator of activation proteinMedicalMentorsMessenger RNAMethodsModelingMusOvarianOvaryOvulationPhasePlasticizersPregnant WomenPrevalenceProcessProductionProgesteroneProstaglandin ProductionProtein AnalysisProteinsPublic HealthQuality of lifeReproductive HealthResearchResearch ProposalsResearch TrainingRodentRodent ModelSamplingSocietiesSolventsTechniquesTestingTimeTissuesToxic Environmental SubstancesToxic effectToxicologyTrainingTranslatingWomananalogangiogenesisbasecareercareer developmentchemical groupcostcyclooxygenase 2exposed human populationfemale fertilitygranulosa cellhuman modelhuman tissuein vivoinsightmigrationmouse modelnovelovarian dysfunctionpersonal care productsphthalatesprogramsreceptorreproductiveresponseskillsurinary
项目摘要
PROJECT SUMMARY/ABSTRACT
This K99/R00 award will prepare Dr. Patrick Hannon for an independent research career, with the main goal of
providing Dr. Hannon all the necessary technical and professional skills to transition into a career in academia
and become a leader in the field of reproductive toxicology. Dr. Hannon has extensive training in elucidating
the effects of environmental toxicants on the ovary in rodent models, but in this K99/R00 he will expand his
research training and translate these findings into human health and fertility. These goals will be accomplished
with the support of Dr. Hannon's enthusiastic and exceptional mentoring team, led by Drs. Thomas Curry and
Humphrey Yao. The research proposal and career development plan created by Dr. Hannon with the guidance
of his mentoring team will provide Dr. Hannon with new experimental techniques and skills needed to establish
an independent research program. In the research training component, Dr. Hannon will elucidate the effects
and mechanisms by which phthalates, a class of endocrine-disrupting chemicals, impair ovulation and fertility
in humans and rodents. Women of reproductive age are exposed to phthalates on a daily basis because
phthalates are incorporated in a myriad of common consumer, medical, building, and personal care products.
However, little is known about the effects of environmentally relevant levels of phthalates on ovulation,
especially in humans. This is concerning because defects in ovulation are the leading cause of infertility in
women. Preliminary data for this proposal are the first to show that an environmentally relevant phthalate
mixture inhibits progesterone (P4) production and alters the mRNA levels of P4 receptor (PGR), prostaglandin-
endoperoxide synthase 2 (PTGS2), and amphiregulin (AREG) following human chorionic gonadotropin
treatment (hCG; analogous to the midcycle luteinizing hormone surge) in human and mouse ovarian cells. P4,
PGR, PTGS2, and AREG are known mediators of ovulation. Thus, these findings suggest that phthalate
exposure may disrupt ovulation contributing to infertility. A primary human granulosa cell model and mice will
be utilized to test the hypothesis that phthalates adversely impact ovulatory processes by altering the levels of
ovulatory mediators leading to impaired ovulation and fertility. Specific Aim 1 (Mentored Phase) will determine
which ovulatory events are impaired by phthalate exposure. Specific Aim 2 (Mentored and Independent
Phases) will elucidate the mechanisms by which phthalates impair these ovulatory processes. Specific Aim 3
(Independent Phase) will establish that phthalate exposure causes impaired ovulation and infertility in vivo.
These findings will establish the impact of phthalates on female fertility and reproductive health, while providing
Dr. Hannon the necessary research and professional skills for his academic career. Further, the attainment of
a greater understanding of the mechanisms of action of phthalates in human samples will begin to provide
avenues to intervene on phthalate-induced reproductive dysfunction and infertility.
项目摘要/摘要
该K99/R00奖将为帕特里克·汉农博士准备独立研究职业,其主要目标是
为汉农博士提供过渡到学术界职业的所有必要的技术和专业技能
并成为生殖毒理学领域的领导者。汉农博士在阐明方面接受了广泛的培训
环境有毒物质对啮齿动物模型中卵巢的影响,但是在此K99/R00中,他将扩大他的
研究培训并将这些发现转化为人类健康和生育能力。这些目标将实现
在汉农博士的热情和杰出的指导团队的支持下,博士领导。托马斯·库里(Thomas Curry)和
Humphrey Yao。 Hannon博士在指导下制定的研究建议和职业发展计划
他的指导团队将为汉农博士提供建立新的实验技术和技能
一个独立的研究计划。在研究培训部分中,汉农博士将阐明影响
以及邻苯二甲酸的机制,一类干扰化学物质的邻苯二甲酸盐,损害排卵和生育
在人类和啮齿动物中。生殖年龄的妇女每天暴露于邻苯二甲酸盐,因为
邻苯二甲酸盐纳入了无数的普通消费者,医疗,建筑和个人护理产品中。
但是,关于环境相关水平邻苯二甲酸盐对排卵的影响知之甚少,
特别是在人类中。这是关于排卵缺陷的主要原因的原因
女性。该提案的初步数据是第一个表明与环境相关的邻苯二甲酸盐的数据
混合物抑制孕酮(P4)的产生,并改变P4受体(PGR),前列腺素 -
在人绒毛膜促性腺激素后
在人和小鼠卵巢细胞中的治疗(HCG;类似于中周期黄体激素激素)。 P4,
PGR,PTGS2和AREG是已知的排卵介质。因此,这些发现表明邻苯二甲酸盐
暴露可能会破坏导致不育的排卵。主要的人颗粒细胞模型和小鼠将
可用于测试邻苯二甲酸的假设,从而通过改变水平来不利地影响排卵过程
排卵介质导致排卵和生育能力受损。特定的目标1(指导阶段)将确定
邻苯二甲酸盐暴露会损害排卵事件。特定目标2(指导和独立
阶段)将阐明邻苯二甲甲化损害这些排卵过程的机制。具体目标3
(独立阶段)将确定邻苯二甲酸盐暴露会导致体内排卵和不育症受损。
这些发现将确定邻苯二甲酸盐对女性生育能力和生殖健康的影响,同时提供
汉农博士的学术生涯必要的研究和专业技能。此外,达到了
对人类样品中邻苯二甲酸酯的作用机制有更深入的了解,将开始提供
干预邻苯二甲酸酯诱导的生殖功能障碍和不育的途径。
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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Patrick Ryan Hannon其他文献
Patrick Ryan Hannon的其他文献
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{{ truncateString('Patrick Ryan Hannon', 18)}}的其他基金
Phthalate-Induced Dysregulation of Prostaglandin and Angiogenic Function During Ovulation in Women
邻苯二甲酸盐引起的女性排卵期间前列腺素和血管生成功能失调
- 批准号:
10358879 - 财政年份:2022
- 资助金额:
$ 24.9万 - 项目类别:
Phthalate-Induced Dysregulation of Prostaglandin and Angiogenic Function During Ovulation in Women
邻苯二甲酸盐引起的女性排卵期间前列腺素和血管生成功能失调
- 批准号:
10544036 - 财政年份:2022
- 资助金额:
$ 24.9万 - 项目类别:
Phthalate-Induced Ovulatory Dysfunction in Women
邻苯二甲酸盐引起的女性排卵功能障碍
- 批准号:
10006568 - 财政年份:2019
- 资助金额:
$ 24.9万 - 项目类别:
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