Placental Genomics in the Developmental Consequences of Marijuana Use in Pregnancy

胎盘基因组学对妊娠期吸食大麻发育后果的影响

基本信息

批准号：
10680973
负责人：
Todd M Everson
金额：
$ 60.38万
依托单位：
MIRIAM HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-06-01 至 2028-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10680973
关键词：
Address Affect Anxiety Architecture Biological Biological Assay Biological Markers Birth Birth Weight Brain Cannabinoids Cannabis Cannabis sativa plant Child Development Collection Communication Data Development Drug usage Endocannabinoids Energy Metabolism Environment Epidemiologic Methods Epigenetic Process Evaluation Fetal Growth Future Gene Expression Genes Genetic Transcription Genomics Goals Growth Health Human Immune Infant Infant Development Intervention Investigation Legal Link Marijuana Mediation Medical Messenger RNA Metabolic Methods Methylation MicroRNAs Molecular Molecular Target Mothers National Institute of Drug Abuse Neurologic Neurons Newborn Infant Organ Outcome Pathway interactions Perception Placenta Play Pregnancy Pregnant Women Prevalence Regulation Reporting Research Risk Role Safety Sampling Screening procedure Seminal Signal Pathway Signal Transduction Strategic Planning Stress Surgeon System Testing United States National Academy of Sciences Untranslated RNA Vascularization Woman Work addiction adipokines biological adaptation to stress biomarker identification brain tissue cohort design epigenetic regulation fetal fetal marijuana exposure fetal tobacco exposure functional genomics gene network genome-wide genomic profiles high risk population immune function implantation improved in utero infant outcome intrauterine environment marijuana legalization marijuana use marijuana use in pregnancy marijuana user maternal marijuana use miRNA expression profiling neurobehavior neurobehavioral neuroblastoma cell neurodevelopment neuron development new therapeutic target novel offspring phenotypic data posttranscriptional pregnant prenatal prenatal exposure prenatal influence prospective sperm cell substance use transcriptome transcriptome sequencing transcriptomic profiling transcriptomics trend

项目摘要

PROJECT SUMMARY/ABSTRACT This application is responsive to NOT-DA-20-039: Effects of Cannabis Use and Cannabinoids on the Devel- oping Brain. Prenatal cannabis use is common and increasing, with rates as high as 1 in 4 in poor, young, underserved women. Expanding legalization of cannabis has led to increasing availability, use, perceptions of safety as well as increased potency. However, data is lacking regarding the impact of prenatal use of increase- ed-potency cannabis on offspring neurodevelopment. Our group is currently conducting an intensive, prospective investigation of the impact of maternal prenatal cannabis use on infant neurodevelopment (R01DA044504). Our ongoing study has yielded preliminary evidence for an impact of prenatal cannabis on offspring growth and neurodevelopment, but does not involve a comprehensive interrogation of genomic pathways underlying these associations. Pinpointing genomic pathways will allow us to identify biomarkers of fetal harm and develop novel screening tools and intervention targets to protect and treat exposed offspring. The placenta is a unique organ that regulates the intrauterine environment, maternal-fetal communication--including passage of cannabinoids--and plays a critical role in supporting fetal growth and neurodevelopment. Seminal work by our group has revealed that the prenatal environment impacts placenta function, that alterations in placenta function can be informed by genomic profiling of the placenta, and that alterations in placenta genomic profiles are linked to newborn growth and neurobehavior. MicroRNAs (miRNAs) are an understudied aspect of placenta epigenetic regulation; miRNAs are short non-coding RNAs that regulate gene expression post-transcriptionally and are crit- ical regulators of placental- and neuro-development. A recent initial study supports the hypothesis that maternal cannabis may impact placenta immune gene networks, and offspring anxiety, but was not designed to investigate prenatal cannabis, only included a small number of cannabis users, and did not include miRNA. We propose a comprehensive placenta miRNA and mRNA profiling study to define the impact of prenatal cannabis exposure on placenta genomic activity and infant neurodevelopment. We test the central hypothesis that prenatal cannabis exposure leads to unique alterations in placenta endocannabinoid, neuronal development, immune, and stress signaling pathways, and that these functional genomic features will also impact infant de- velopment. We leverage our ongoing cohort (n=100 cannabis users, n=100 non-users) designed to assess the impact of prenatal cannabis on infant neurodevelopment and including placenta collection for candidate methyl- ation assays. Our proposed genomic mechanisms study involves the addition of state-of-the-art whole transcrip- tome RNA-sequencing (mRNA and miRNA) to delineate the functional impacts of prenatal cannabis exposure and links to infant development. Determining genomic profiles underlying the impact of prenatal cannabis on infant development is timely and offers potential to identify biomarkers of exposure and offspring risk as well as molecular targets for future intervention efforts.

项目摘要/摘要该应用对NOT-DA-20-039的响应：大麻使用和大麻素对Devel的影响 - 大脑。使用产前大麻是常见的，而且增加，贫穷，年轻，年龄高达4分之一服务不足的妇女。扩大大麻合法化已导致可用性，使用，对安全性和增加的效力。但是，缺乏关于在产前使用增加的影响的数据 - 在后代神经发育的ED功能大麻。我们的小组目前正在进行密集，潜在的研究母体产前大麻对婴儿神经发育的影响（R01DA044504）。我们的正在进行的研究提供了初步证据证明产前大麻对后代增长和神经发育，但不涉及对这些基因组途径的全面审讯协会。精确的基因组途径将使我们能够识别出胎儿伤害的生物标志物并发展新颖的筛查工具和干预目标，以保护和治疗暴露的后代。胎盘是调节宫内环境的独特器官，孕产妇的交流 - 包括大麻素 - 并且在支持胎儿生长和神经发育方面起着至关重要的作用。我们的开创性工作小组揭示了产前环境会影响胎盘功能，胎盘功能的改变可以通过胎盘的基因组分析来告知，并且胎盘基因组轮廓的改变是联系的到新生儿的生长和神经行为。 microRNA（miRNA）是胎盘表观遗传学的研究规定; miRNA是简短的非编码RNA，在转录后调节基因表达并进行批判 - 胎盘和神经发展的iCal调节剂。最近的一项初步研究支持了母体的假设大麻可能会影响胎盘免疫基因网络和后代焦虑，但并非旨在调查产前大麻仅包括少数大麻使用者，不包括mirna。我们提出了一个综合胎盘miRNA和mRNA分析研究，以定义产前大麻的影响胎盘基因组活性和婴儿神经发育的暴露。我们检验了一个中心假设产前大麻暴露会导致胎盘内源性大麻素的独特改变，神经元发育，免疫和应力信号通路，这些功能基因组特征也会影响婴儿速度。我们利用我们正在进行的队列（n = 100个大麻使用者，n = 100个非用户），旨在评估产前大麻对婴儿神经发育的影响，包括用于候选甲基的胎盘收集 ation分析。我们提出的基因组机制研究涉及添加最先进的整个transcrip- TOME RNA序列（mRNA和miRNA）描述产前大麻暴露的功能影响并链接到婴儿发育。确定产前大麻对影响的基因组概况婴儿发育是及时的，并提供了识别暴露和后代风险的生物标志物以及未来干预工作的分子目标。