Department of Urology, McGill University Health Centre, Montreal, QC, Canada.
Department of Pharmacology & Therapeutics, McGill University, Montreal, QC, Canada.
Front Endocrinol (Lausanne). 2022 Jun 9;13:897101. doi: 10.3389/fendo.2022.897101. eCollection 2022.
Paternal age at conception has been increasing. In this review, we first present the results from the major mammalian animal models used to establish that increasing paternal age does affect progeny outcome. These models provide several major advantages including the possibility to assess multi- transgenerational effects of paternal age on progeny in a relatively short time window. We then present the clinical observations relating advanced paternal age to fertility and effects on offspring with respect to perinatal health, cancer risk, genetic diseases, and neurodevelopmental effects. An overview of the potential mechanism operating in altering germ cells in advanced age is presented. This is followed by an analysis of the current state of management of reproductive risks associated with advanced paternal age. The numerous challenges associated with developing effective, practical strategies to mitigate the impact of advanced paternal age are outlined along with an approach on how to move forward with this important clinical quandary.
父亲的生育年龄一直在增加。在这篇综述中，我们首先介绍了主要用于证实父亲年龄增加确实会影响后代的结果的几种主要哺乳动物动物模型的研究结果。这些模型提供了多个主要优势，包括在相对较短的时间窗口内评估父亲年龄对后代的多代际影响的可能性。然后，我们介绍了与高龄父亲生育能力和对后代围产期健康、癌症风险、遗传疾病和神经发育影响相关的临床观察。介绍了高龄时改变生殖细胞的潜在机制的概述。接下来分析了与高龄生育相关的生殖风险的当前管理状态。概述了与制定有效、实用的策略来减轻高龄生育的影响相关的众多挑战，并提出了如何解决这一重要临床难题的方法。
