Placental epigenetic mechanisms contributing to sex-specific impacts of maternal stress on fetal development
Placental epigenetic mechanisms contributing to sex-specific impacts of maternal stress on fetal development
批准号:
10743792
负责人:
Tracy L Bale
金额:
$27.15万
依托单位国家:
美国
项目类别:
财政年份:
2019
资助国家:
美国
项目状态:
已结题
起止时间:
2019-03-11 至 2024-02-29
中文摘要
确定怀孕期间环境中的压力促进改变的机制
英文摘要
Defining the mechanisms by which stress in the environment during pregnancy promotes changes in
development is critical in identifying factors predictive of disease risk or resilience. One major consistency
across prenatal insults is the increased vulnerability of males. In this proposal, we utilize our mouse model of
early prenatal stress (EPS) to examine sex-specific placental transcriptional regulation. In our EPS model,
male, but not female, offspring present with increased stress sensitivity, including increased HPA stress axis
activity, reduced post-weaning growth, and hypothalamic mitochondrial dysfunction. Sex differences in the
placental function are likely to produce sex-specific transplacental signals to the developing fetal brain. Sex
differences in the placenta begin with sex chromosomes. Through a genome-wide screen following maternal
stress, we identified the X-linked gene, OGT, as causal in programming the male-specific stress phenotype via
its regulation of the histone transcriptional repressive mark, H3K27me3. This proposal uses innovative
approaches to determine the mechanisms by which the female placenta is able to restrict transcriptional
responses to stress in the environment, where males are not, thus placing the male developing brain at greater
risk prenatally. The transplacental signals received by the developing brain appear to be related to energy
availability and impact metabolic and mitochondrial programming. Of key translational importance, we have
also found the same biochemical and molecular outcomes are predicted by fetal sex in human placental tissue.
Therefore, our proposal will focus on defining the causal importance of H3K27me3 in risk for developmental
changes in response to stress, identify the sex-specific transplacental signals resulting from these changes in
placental function using ex vivo perfusion, and determine the cellular compartment and mechanism by which
these changes promote hypothalamic mitochondrial reprogramming and the EPS phenotype.
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Placental epigenetic mechanisms contributing to sex-specific impacts of maternal stress on fetal development
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Placental epigenetic mechanisms contributing to sex-specific impacts of maternal stress on fetal development
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Placental epigenetic mechanisms contributing to sex-specific impacts of maternal stress on fetal development
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Placental epigenetic mechanisms contributing to sex-specific impacts of maternal stress on fetal development
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批准号:10563162
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资助金额:$52.36万
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负责人:Tracy L Bale
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依托单位:
Female preconception stress programming of offspring neurodevelopment
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批准号:9360959
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资助金额:$45.59万
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财政年份:2017
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负责人:Tracy L Bale
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Female preconception stress programming of offspring neurodevelopment
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批准号:10163188
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资助金额:$43.65万
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财政年份:2017
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负责人:Tracy L Bale
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依托单位:
Paternal stress epigenetic programming of offspring neurodevelopment
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批准号:9118382
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资助金额:$57.05万
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财政年份:2015
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负责人:Tracy L Bale
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依托单位:
Paternal stress epigenetic programming of offspring neurodevelopment
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批准号:10431811
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项目类别:
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资助金额:$25.99万
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财政年份:2015
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负责人:Tracy L Bale
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依托单位:
Paternal stress epigenetic programming of offspring neurodevelopment
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批准号:10083903
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项目类别:
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资助金额:$63.66万
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财政年份:2015
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负责人:Tracy L Bale
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依托单位:
Maternal stress and the vaginal microbiome: impacts on brain development
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批准号:9332193
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项目类别:
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资助金额:$67.06万
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财政年份:2014
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负责人:Tracy L Bale
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依托单位:
Maternal stress and the vaginal microbiome: impacts on brain development
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批准号:8749104
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项目类别:
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资助金额:$28.0万
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财政年份:2014
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负责人:Tracy L Bale
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依托单位:
Early pregnancy stress programming of offspring emotionality
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批准号:7985385
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项目类别:
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资助金额:$40.0万
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财政年份:2010
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负责人:Tracy L Bale
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依托单位:
Early pregnancy stress programming of offspring emotionality
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批准号:8257959
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项目类别:
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资助金额:$39.6万
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财政年份:2010
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负责人:Tracy L Bale
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依托单位:
Early Gestation as a Sensitive Period to Stress in Sex-Dependent Neurodevelopment
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批准号:8619658
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项目类别:
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资助金额:$39.6万
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财政年份:2010
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负责人:Tracy L Bale
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依托单位:
Early pregnancy stress programming of offspring emotionality
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批准号:8120977
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项目类别:
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资助金额:$39.6万
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财政年份:2010
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负责人:Tracy L Bale
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依托单位:
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