Investigating The Role Of The Maternal Androgen Milieu On Placental Function: A Potential Mechanism For Programming Of Fetal Growth Restriction And Cardiometabolic Dysregulation In Adulthood
研究母体雄激素环境对胎盘功能的作用:胎儿生长受限和成年期心脏代谢失调的潜在机制
基本信息
- 批准号:10347630
- 负责人:
- 金额:$ 8.95万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-03-01 至 2024-02-29
- 项目状态:已结题
- 来源:
- 关键词:AddressAdultAdult ChildrenAdverse effectsAnatomyAndrogen ReceptorAndrogensBirthBirth WeightBlindedBlood CirculationBlood VesselsCardiometabolic DiseaseCardiovascular DiseasesChildhoodComplementDataData AnalysesDevelopmentEndocrineExposure toFamiliarityFamily StudyFemaleFetal GrowthFetal Growth RetardationFetusFunctional disorderFundingFutureGoalsGonadal Steroid HormonesGrowthGrowth and Development functionHealthHormonesHospitalsHumanHypertensionImmunologicsImpairmentLeadLesionLifeLife Cycle StagesLongevityLongitudinal cohortLongitudinal cohort studyLow Birth Weight InfantMeasuresMediatingMedicineMetabolicMetabolic DiseasesMetabolic Syndrome XMetabolic syndromeMissionModelingMothersNational Heart, Lung, and Blood InstituteNew EnglandNutrientOrganOutcomeOutcome MeasureOxygenParticipantPathologicPathologistPathologyPerinatalPlacentaPlacental InsufficiencyPlayPre-Clinical ModelPregnancyPregnant WomenResearchResearch ProposalsRiskRisk FactorsRoleSerumSex DifferencesSurrogate MarkersSystemTestosteroneTherapeuticThird Pregnancy TrimesterTissuesVascular resistanceVascularizationWeightWomanandrogen excessbasecardiometabolic riskcardiometabolismcardiovascular disorder riskcritical developmental periodepigenetic markerfetalfetal programmingfetus hypoxiafollow-uphealth of the motherhuman modelimprovedin uterolongitudinal analysismalemedical schoolsnew therapeutic targetoffspringplacental morphologypreclinical studyprenatalprenatal exposureprenatal influenceprofessorprogramsresponsesecondary analysissexwasting
项目摘要
Project Summary
Early prenatal exposure to sex steroids in utero has been shown to alter fetal developmental
trajectory and induce cardiometabolic pathologies in adulthood. Several preclinical studies have
shown that maternal androgen exposure is associated with reduced fetal growth and development of
cardiometabolic disorders in the adult offspring. During pregnancy, the placenta is the main organ
supplying nutrients, oxygen, and hormones from mother to fetus. Indeed, adverse fetal outcomes and
programming of long-term health risks are known to have placental origins. Given that androgen
receptors are expressed in human placenta, it has been proposed that androgens can modify normal
placental function. Thus, these observations highlight the plausibility of placental compromise in
pregnancies exposed to excess androgens, which may be a mechanism for programming of fetal
growth restriction and subsequent cardiometabolic dysregulation in adult life
This research proposal will investigate the relationship of maternal androgens during pregnancy with
pathologic markers of placental function and determine their impact on predicting cardiometabolic
diseases in adulthood among mother-offspring New England participants of the historic Collaborative
Perinatal Project (1959-1966). Given the sex differences in the anatomy and growth of the placenta, it
is also imperative to understand how changes in placental function impacts male versus female
offspring in response to prenatal androgen exposure. Thus, this proposal will also investigate the sex
differences in the effects of prenatal androgens on the placenta which has not be adequately
addressed in previous studies. Understanding the influence of prenatal androgens on the placental
system could lead to new sex-specific therapeutic approaches to target placental dysfunctions during
pregnancy and improve the health of mothers and their offspring across the lifespan.
Dr. Grace Huang (the PI) is an Assistant Professor of Medicine at Brigham and Women’s Hospital
and Harvard Medical School. Her K08 studies have already provided longitudinal evidence in a
human model that alterations in the gestational androgen milieu can have life-long programming
effects on the metabolic health of the offspring that is sex-dependent. The proposed R03 project will
build upon these findings and examine the sex-dependent impact of prenatal androgens on the
placenta, as a potential mechanism for long-term programming of adult cardiometabolic diseases.
These will be secondary analyses of data already collected that the PI has access to and familiarity
with analyzing. Together, the results of these studies will provide strong preliminary data supporting
an R01 application to further investigate the androgen-mediated mechanisms and epigenetic markers
involved in early programming of adult CVD and their underlying sex differences across the lifespan.
项目摘要
研究表明,产前早期在子宫内接触性激素会改变胎儿的发育
在成年期跟踪和诱导心脏代谢病理。一些临床前研究已经
研究表明,母亲接触雄激素与胎儿生长和发育减少有关
成年后代的心脏代谢障碍。在怀孕期间,胎盘是主要的器官
从母亲向胎儿提供营养、氧气和激素。事实上,不良的胎儿结局和
众所周知,对长期健康风险的规划源于胎盘。考虑到雄激素
受体在人胎盘中表达,已有研究表明雄激素可以改变正常
胎盘功能。因此,这些观察结果突出了胎盘妥协的合理性
妊娠暴露于过量雄激素,这可能是一种规划胎儿
成年后的生长受限和随后的心脏代谢紊乱
这项研究计划将调查怀孕期间母体雄激素与
胎盘功能的病理标志物及其对心脏代谢预测的影响
新英格兰参加历史性合作的母子成年期的疾病
围产期计划(1959-1966)。鉴于胎盘在解剖和生长方面的性别差异,它
了解胎盘功能的变化对男性和女性的影响也是非常必要的
子代对产前雄激素暴露的反应。因此,这项建议还将调查性别
产前雄激素对胎盘影响的差异
在以前的研究中解决了这些问题。了解产前雄激素对胎盘的影响
系统可以导致新的针对性别的治疗方法来针对胎盘功能障碍
怀孕和改善母亲及其子女一生的健康。
格蕾丝·黄博士是布里格姆妇女医院的医学助理教授
和哈佛医学院。她的K08研究已经提供了纵向证据
孕期雄激素环境的改变可能会有终生编程的人类模型
对性别依赖的后代的代谢健康的影响。拟议的R03项目将
在这些发现的基础上,研究产前雄激素对性别的影响
胎盘,作为成人心脏代谢性疾病长期规划的潜在机制。
这些将是对PI有权访问和熟悉的已收集数据的二次分析
通过分析。总之,这些研究的结果将提供强有力的初步数据支持
R01在进一步研究雄激素介导的机制和表观遗传标记中的应用
参与了成人心血管疾病的早期规划以及他们在整个生命周期中潜在的性别差异。
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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Grace Huang其他文献
Grace Huang的其他文献
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{{ truncateString('Grace Huang', 18)}}的其他基金
A Pilot Study to Evaluate the Anabolic Effect of Testosterone on Muscles of the Pelvic Floor in Older Women with Stress Urinary Incontinence
评估睾酮对患有压力性尿失禁的老年女性盆底肌肉合成代谢影响的初步研究
- 批准号:
10716432 - 财政年份:2023
- 资助金额:
$ 8.95万 - 项目类别:
Investigating The Role Of The Maternal Androgen Milieu On Placental Function: A Potential Mechanism For Programming Of Fetal Growth Restriction And Cardiometabolic Dysregulation In Adulthood
研究母体雄激素环境对胎盘功能的作用:胎儿生长受限和成年期心脏代谢失调的潜在机制
- 批准号:
10571932 - 财政年份:2022
- 资助金额:
$ 8.95万 - 项目类别:
Prenatal Androgens and Cardiometabolic Risk in Adulthood
产前雄激素和成年后的心脏代谢风险
- 批准号:
9898427 - 财政年份:2017
- 资助金额:
$ 8.95万 - 项目类别:
Testosterone Dose-Response on Cardiometabolic Outcomes in Surgically Menopausal W
睾酮剂量反应对手术绝经 W 患者心脏代谢结果的影响
- 批准号:
8596189 - 财政年份:2013
- 资助金额:
$ 8.95万 - 项目类别:
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