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

项目摘要/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著的变化 富裕国家导致生育的时间越来越晚。除了……之外 随着年龄的增长，生育力的下降，有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。这通常被归因于 父性高龄对精子遗传变化的影响 敬孩子们。在这里，我们考虑了一种被低估的可能性--老龄化过程 影响精子携带的表观遗传信息，从而导致“表观突变” 对下一代出现的改变的表型负责。 在这里，我们建议调查衰老对关键男性生殖的影响 组织，包括睾丸、附睾、精囊和前列腺。我们将探索 高龄父亲对儿童多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 从幼年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 生殖功能和对后代的影响，并可能提供治疗途径 以减轻延迟亲子关系对儿童疾病风险的影响。

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.