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：
10272452
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/10272452
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 Partner in relationship Paternal Age Phenotype Population Pre-implantation Embryo Development Prevalence Process Prostate 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 public health relevance reproductive reproductive function reproductive tract single-cell RNA sequencing sperm cell trait transcriptome sequencing 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.

项目概要/摘要在过去的一个世纪里，美国和其他国家的人口结构发生了显着的变化富裕国家导致生育晚年和晚年。随着年龄的增长，生育能力下降，越来越多的证据表明父亲的年龄会影响后代的健康和疾病。高龄父亲对传递的精子遗传变化的影响在这里，我们考虑一个未被充分认识的可能性——衰老过程。影响精子中携带的表观遗传信息，从而产生“表观突变” 负责在下一代中表现出的表型改变。在这里，我们建议研究衰老对关键男性生殖的影响我们将探索睾丸、附睾、精囊和前列腺等组织。高龄父亲对各种行为和代谢特征的影响后代，并将全面分析精子之间的分子差异从年轻和年老的动物身上获得。总之，这些实验系统地解决了衰老对男性的影响生殖功能和后代，并可能提供治疗途径减轻延迟生育对儿童疾病风险的影响。