Effects of paternal aging on male reproductive biology and on future generations

父亲衰老对男性生殖生物学和后代的影响

基本信息

批准号：
10624353
负责人：
OLIVER J RANDO
金额：
$ 50.89万
依托单位：
UNIV OF MASSACHUSETTS MED SCH WORCESTER
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-08-15 至 2026-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10624353
关键词：
Address Adult Affect Age Age Months Aging Animals Behavior Behavioral Caloric Restriction Cell physiology Cells Child Conceptions Country Couples Cytosine Data Set Development Disease Elderly Epididymis Epigenetic Process Female Fertility Follow-Up Studies Foundations Future Future Generations Genes Genetic Transcription Genomics Goals Health Histologic Histones Human Inbred Mouse Individual Intervention Lead Life Life Style Measurement Metabolic Metabolism Methylation Modeling Molecular Mouse Strains Mus Mutation Neurodevelopmental Disorder Partner in relationship Paternal Age Phenotype Population Pre-implantation Embryo Development Prevalence Process Prostate Public Health RNA Reproductive Biology Resolution Risk Seminal Vesicles Surveys Testis Therapeutic Time Tissues United States Western World age effect behavioral phenotyping career cell type child bearing disorder risk epigenome epigenomics experimental study father role genome-wide analysis genomic platform innovation male metabolic phenotype neurodevelopment neuropsychiatric disorder next generation offspring older men reproductive reproductive function reproductive tract single-cell RNA sequencing sperm cell trait transcriptome sequencing transmission process zygote

项目摘要

Project Summary/Abstract Over the past century, a marked demographic shift in the United States and other wealthy countries has lead to childbearing occurring later and later in life. In addition to the decrease in fecundity that accompanies aging, there is accumulating evidence that paternal age can impact offspring health and disease. This has typically been attributed to the effects of advanced paternal age on genetic changes in sperm that are transmitted to children. Here, we consider an underappreciated possibility – that the aging process affects epigenetic information carried in sperm, with resulting “epimutations” being responsible for the altered phenotypes that manifest in the next generation. Here, we propose to investigate the effects of aging on key male reproductive tissues, including the testis, epididymis, seminal vesicle, and prostate. We will explore the effects of advanced paternal age on a variety of behavioral and metabolic traits in offspring, and will comprehensively analyze molecular differences between sperm obtained from young and old animals. Together, these experiments systematically address the effects of aging on male reproductive function and on future generations, and may provide therapeutic avenues for mitigating the effects of delayed paternity on disease risk in children.

项目摘要/摘要在过去的一个世纪中，美国和其他人的人口转变明显富裕的国家导致生命较晚和晚年发生。此外涉及衰老的繁殖力的下降，有积累的证据表明父亲的年龄会影响后代的健康和疾病。这通常是归因于晚期父亲年龄对传播精子的遗传变化的影响给孩子。在这里，我们认为一种可能性不足的可能性 - 衰老过程影响精子中携带的表观遗传信息，导致的“表述”是负责下一代体现的改变的表型。在这里，我们建议研究衰老对关键男性生殖的影响组织，包括睾丸，附睾，半叶子和前列腺。我们将探索晚期父亲时代对各种行为和代谢性状的影响后代，并将全面分析精子之间的分子差异从年轻和老动物获得。这些实验共同解决了衰老对男性的影响生殖功能和子孙后代，并可能提供治疗途径用于减轻延迟亲子关系对儿童疾病风险的影响。