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Epigenetic Mechanisms Mediating the Inheritance of Reproductive Behavior

介导生殖行为遗传的表观遗传机制

基本信息

批准号：
7429568
负责人：
FRANCES A. CHAMPAGNE
金额：
$ 241.5万
依托单位：
COLUMBIA UNIV NEW YORK MORNINGSIDE
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-09-30 至 2012-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7429568
关键词：
Academic Training Accounting Acetates Adaptive Behaviors Address Adolescent Adrenal Glands Adult Adult Children Age Aggressive behavior Air Aloe Amides Amygdaloid structure Animal Behavior Animal Husbandry Animal Model Animals Anxiety Area Automobile Driving Autoradiography Bacitracin Base Sequence Beds Behavior Behavioral Binding Birth Bite Boxing Brain Brain region Brain-Derived Neurotrophic Factor Buffers Caloric Restriction Cannulas Cannulations Caring Categories Cells Chemicals Child Childhood Chloroform Chromatin Structure Cloning Code Cognition Computer Assisted Condition Cues Cytosine Cytosine Nucleotides DNA DNA Methylation DNA Modification Process DNA Structure DNA-Directed RNA Polymerase Daily Data Data Collection Data Set Data Sources Daughter Decapitation Dedications Densitometry Dental Cements Development Diet Discipline of Nursing Dopamine Eating Ejaculation Emotional Endocrinology Endoribonucleases Energy Intake Environment Environmental Risk Factor Epigenetic Process Estrogen Receptor alpha Estrogen Receptors Estrogens Estrus Ethanol Evaluation Evolution Excision Exhibits Experimental Designs Experimental Models Exploratory Behavior Exposure to Feedback Female Film Floor Food Fostering Freezing Frequencies Future Gel Gene Activation Gene Expression Gene Expression Profile Gene Expression Regulation Gene Silencing Generations Genes Genetic Genome Glucocorticoid Receptor Goals Grooming Growth Hippocampus (Brain)Histones Home environment Hospitals Hour Housing Human Human Resources Humulus Hydroquinones Hypothalamic structure Immediate-Early Genes Implant In complete remission Incubated Individual Individual Differences Infant Infusion procedures Injection of therapeutic agent International Investigation Investments Ketamine Label Laboratories Lactation Late Effects Lateral Left Legal patent Life Light Lighting Literature Long-Evans Rats Long-Term Effects Lordosis Lysine Mammals Manuscripts Maps Maternal Behavior Measures Medial Mediating Mediation Mediator of activation protein Mentorship Messenger RNA Methionine Methodology Methods Methylation Microdialysis Middle Hypothalamus Modeling Modification Molecular Molecular Analysis Monitor Mothers Mus Nature Nerve Growth Factors Nested PCR Neurosciences Neurosecretory Systems Nucleosome Core Particle Nucleus Accumbens Numbers Nurses Odors Optics Organism Outcome Output Oxytocin Oxytocin Receptor Pancreatic ribonuclease Partner in relationship Patient currently pregnant Pattern Patterns of Care Personal Satisfaction Pharmaceutical Preparations Phase Phenotype Phosphate Buffer Physiology Pituitary Gland Planet Mars Plasmids Plastics Play Plexiglas Plexiglass Polymerase Chain Reaction Population Postpartum Period Posture Predatory Behavior Pregnancy Preoptic Areas Primates Procedures Process Production Promoter Regions Proteins Protocols documentation Psychiatry Psychology Psychopathology Publishing Purpose Quality of Care Range Rattus Reaction Reading Receptor Gene Recovery Regulation Relative (related person)Reporting Reproduction Reproductive Behavior Reproductive Periods Research Research Personnel Research Project Grants Rest Retrieval Ribonucleases Risk Rodent Rodent Model Role Saline Science Score Secure Series Sex Behavior Shapes Side Signal Pathway Site Slice Slide Social Behavior Social Environment Social Interaction Socialization Sodium Solutions Source Specific qualifier value Specificity Staging Stainless Steel Standards of Weights and Measures Steel Stimulus Stress Structure of terminal stria nuclei of preoptic region Study models Supplementation Surface Swab System Tactile Techniques Temperature Testing Time Tissue Extracts Tissues Training Transfer RNA Translating Trichostatin A Tromethamine Universities Vagina Variant Video Recording Water Weaning Week Work acetic anhydride animal facility base behavior influence behavior measurement behavioral/social science biological adaptation to stress brain tissue cRNA Probes career chemical bond cohort concept cost day density design desire drinking early experience experience field study fighting food restriction hydroquinone hypothalamic-pituitary-adrenal axis in vivo infancy innovation insight interest male maternal separation member methyl group model development mouse model neurobiological mechanism next generation non-genomic novel novel strategies paraform post-doctoral training postnatal prevent programs promoter pup receptor receptor binding receptor expression reproductive reproductive development research study response restraint stress seal sex size skills social social skills social stress sodium bisulfite theories tool trait transcription factor transmission process treatment effect triethanolamine young adult

项目摘要

Natural variations in mother-infant interaction have profound effects on offspring development and behavior. In particular, there is evidence for the influence of postpartum care on maternal behavior itself, such that low levels of maternal care are exhibited by females who received less care in infancy. This transmission of maternal behavior from mother to daughter has been previously associated with epigenetic regulation of estrogen receptor (ER) α in hypothalamic brain regions. The purpose of the proposed project is to explore these epigenetic effects in the context of reproductive behavior and develop convergent sources of evidence for the transgenerational influence of maternal care. To achieve this goal, the maternal regulation of social, sexual and maternal behavior will be explored in a rodent model. This will provide an experimental design for determining potential shifts in reproductive strategy in response to early environmental experiences. The reversibility of these maternal effects will be explored through pharmacological manipulation of DNA methylation within the promoter region of the ERα gene. The role of DNA methylation in the generational transmission of environmental experiences that occur beyond the postpartum period will also be investigated in response to gestational stress and juvenile exposure to differential levels of social interaction. Finally, ecologically valid paradigms will be developed in which transgenerational effects on reproductive behavior can be determined in a mouse model. These paradigms will involve 1) comparison of communally vs. non-communally reared offspring and grand-offspring, 2) caloric food restriction during lactation and 3) comparison of offspring born to either inexperienced or experienced mothers. Overall, this project will provide an innovative approach to both the study of inheritance and the role of epigenetic mechanisms in sustaining environmental effects within and across generations. Moreover, it will provide an experimental design for elucidating the occurrence of reproductive trade-offs in mammals.

母婴互动的自然变化对后代的发育有着深远的影响和行为。特别是，有证据表明产后护理对产妇的影响行为本身，因此接受较少的母亲护理的女性表现出低水平婴儿期的护理。这种母性行为从母亲到女儿的传递先前与下丘脑雌激素受体 (ER) α 的表观遗传调控有关大脑区域。拟议项目的目的是探索这些表观遗传效应生殖行为的背景，并为生殖行为开发汇聚证据来源孕产妇护理的跨代影响。为了实现这一目标，母亲的调节将在啮齿动物模型中探讨社会、性和母性行为。这将提供一个确定生殖策略潜在变化的实验设计，以应对早期环境经验。这些母体效应的可逆性将通过以下方式进行探索： ERα 基因启动子区域 DNA 甲基化的药理学操作。 DNA甲基化在环境经验代际传递中的作用产后期间发生的情况也将被调查以应对妊娠应激以及青少年接触不同程度的社会互动的情况。最后，生态有效将开发范式，其中可以研究对生殖行为的跨代影响在小鼠模型中确定。这些范式将涉及 1) 公共与非公共的比较。非共同饲养的后代和孙代，2）哺乳期热量食物限制 3）比较经验不足或经验丰富的母亲所生的后代。全面的，该项目将为遗传研究和遗传作用提供创新方法维持代内和代际环境影响的表观遗传机制。此外，它将提供一个实验设计来阐明生殖的发生哺乳动物的权衡。

项目成果

期刊论文数量（24）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Concordance in hippocampal and fecal Nr3c1 methylation is moderated by maternal behavior in the mouse.

DOI：
10.1002/ece3.416
发表时间：
2012-12
期刊：
ECOLOGY AND EVOLUTION
影响因子：
2.6
作者：
Liberman, Shayna A.;Mashoodh, Rahia;Thompson, Robert C.;Dolinoy, Dana C.;Champagne, Frances A.
通讯作者：
Champagne, Frances A.

Maternal modulation of paternal effects on offspring development.