Characterizing effects of sperm- and oocyte-derived epigenetic factors on early embryonic gene expression and offspring metabolic function
精子和卵母细胞衍生的表观遗传因子对早期胚胎基因表达和后代代谢功能的影响
基本信息
- 批准号:10319616
- 负责人:
- 金额:$ 3.17万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-01-05 至 2023-01-04
- 项目状态:已结题
- 来源:
- 关键词:AddressAdultAdult ChildrenAffectBiological ModelsBrown FatCellsCommunicationDNADevelopmentDietDiseaseDisease susceptibilityEducational process of instructingEducational workshopEmbryoEmbryologyEmbryonic DevelopmentEnsureEnvironmentEnvironmental ImpactEnvironmental Risk FactorEpidemicEpigenetic ProcessFathersFatty acid glycerol estersFellowshipFemaleFertilization in VitroFetal DevelopmentFosteringGene ExpressionGeneticGenetic TranscriptionGenetic studyGerm CellsHealthHigh Fat DietIn VitroIndividualInheritedInsulin ResistanceKnowledgeLifeLife StyleLinkLiverMammalsMassachusettsMaternal-Fetal ExchangeMentorsMetabolicMetabolic DiseasesMetabolismMicroRNAsMicroinjectionsModelingMolecularMorulaMothersMusNutrientObesityOocytesPancreasParentsParthenogenesisPhenotypePlacentaPopulationPredispositionPregnancyPrevention strategyProtein-Restricted DietProteinsRNAResearchRiskScienceSideSkeletal MuscleSmall RNAStainsStimulusSurrogate MothersTechniquesTestingTissuesTrainingTransfer RNAUniversitiesWorkbaseblastocystcareer developmentdietarydietary controldifferential expressionenvironmental stressorexperienceexperimental studygenetic informationglucose tolerancegraduate studentimprovedinsightinsulin toleranceintergenerationalmalemedical schoolsmetabolic phenotypemother nutritionnon-geneticoffspringresponsesperm cellsperm functionsymposiumtranscriptometranscriptome sequencingtranscriptomicstransmission processzygote
项目摘要
PROJECT SUMMARY/ABSTRACT
Metabolic diseases such as obesity have become significant health risks affecting one-third of the population
worldwide and can have devastating complications. It is therefore imperative to understand the causes of
metabolic disease predisposition in order to develop preventative strategies. Extensive genetic studies have
failed to explain this ongoing epidemic. However, parents pass on not only genetic information, but also
epigenetic factors, which can be modified in response to environmental stimuli, and can then affect gene
expression. If information about parental environment can be recorded in the germline, it has the potential to be
transmitted to the zygote and impact offspring health. This concept remains controversial in mammals and
represents a large knowledge gap in the field of embryology. Previous work in the lab has demonstrated that
sperm from fathers fed a low protein diet carry tRNA fragments and microRNAs that can modify gene expression
in the embryo. Therefore, in Aim 1, sperm-derived RNAs will be purified and microinjected into
parthenogenetically-activated oocytes, or parthenotes, which lack any paternal genetic content.
Transcriptomic profiles of injected parthenotes will be acquired by single-embryo RNA-Seq to
characterize resulting alterations to the embryonic transcriptome. Maternal transmission of epigenetic
information has not been characterized to the same extent as the paternal side. Therefore, in Aim 2 a similar
dietary paradigm will be utilized to address the question of whether information about maternal diet can
be carried in oocytes and result in changes to the embryonic transcriptome. In vitro-fertilized embryos
from mothers fed low protein, high fat, or control diet will be sequenced by single-embryo RNA-Seq.
These embryos will be transferred to foster mothers to produce adult offspring, which will then be
assessed for glucose tolerance and insulin resistance. The use of in vitro fertilization in this paradigm will
ensure that any changes observed in the embryo originate from the oocyte and not from nutrient exchange during
gestation. Completion of this research will elucidate effects of paternal and maternal epigenetic factors carried
by gametes on the embryonic transcriptome.
This work will be completed at the University of Massachusetts Medical School under the sponsorship of Dr.
Oliver Rando. The fellowship training plan includes training in embryological techniques, such as microinjection
and immunofluorescent staining of lineage markers, as well as metabolic phenotyping of adult mice.
Opportunities to gain experience in science communication include participation in departmental seminars and
local and national conferences. Furthermore, career development workshops are provided by the university, in
addition to teaching and mentoring of first-year graduate students.
项目总结/摘要
肥胖等代谢性疾病已成为影响三分之一人口的重大健康风险
世界范围内,并可能有毁灭性的并发症。因此,必须了解
代谢性疾病的易感性,以制定预防策略。广泛的遗传学研究
无法解释这种持续的流行病然而,父母不仅传递遗传信息,
表观遗传因素,它可以在对环境刺激的反应中被修改,然后可以影响基因,
表情如果有关父母环境的信息可以记录在生殖系中,那么它就有可能被遗传。
传染给受精卵并影响后代的健康。这一概念在哺乳动物中仍然存在争议,
代表了胚胎学领域的一个巨大的知识缺口。实验室先前的工作已经证明,
来自低蛋白饮食父亲的精子携带可以改变基因表达的tRNA片段和microRNA
在胚胎中。因此,在目标1中,将纯化精子来源的RNA并显微注射到
孤雌激活的卵母细胞,或孤雌生殖,缺乏任何父系遗传内容。
将通过单胚胎RNA-Seq获得注射的单性生殖体的转录组学谱,
表征胚胎转录组的改变。表观遗传的母体传递
信息的特点没有达到与父亲一方相同的程度。因此,在目标2中,
饮食范例将被用来解决有关母亲饮食的信息是否可以
携带在卵母细胞中并导致胚胎转录组的变化。体外受精胚胎
来自饲喂低蛋白、高脂肪或对照饮食的母亲的胚胎将通过单胚胎RNA-Seq进行测序。
这些胚胎将被转移到寄养母亲,以产生成年后代,然后将被
评估葡萄糖耐量和胰岛素抵抗。在这种模式下,体外受精的使用将
确保在胚胎中观察到的任何变化都来自卵母细胞,而不是来自营养交换。
怀孕这项研究的完成将阐明父亲和母亲的表观遗传因素的影响,
通过胚胎转录组上的配子。
这项工作将在马萨诸塞州大学医学院完成。
奥利弗兰多。研究金培训计划包括胚胎学技术培训,如显微注射
谱系标记的免疫荧光染色以及成年小鼠的代谢表型。
获得科学传播经验的机会包括参加部门研讨会,
地方和国家会议。此外,大学还提供职业发展讲习班,
除了教学和指导一年级的研究生。
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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Marina Krykbaeva其他文献
Marina Krykbaeva的其他文献
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{{ truncateString('Marina Krykbaeva', 18)}}的其他基金
Characterizing effects of sperm- and oocyte-derived epigenetic factors on early embryonic gene expression and offspring metabolic function
精子和卵母细胞衍生的表观遗传因子对早期胚胎基因表达和后代代谢功能的影响
- 批准号:
9909811 - 财政年份:2020
- 资助金额:
$ 3.17万 - 项目类别:
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