Biol Reprod. 2022 Jan 13;106(1):58-65. doi: 10.1093/biolre/ioab202.
Delayed parenthood is constantly increasing worldwide due to various socio-economic factors. In the last decade, a growing number of epidemiological studies have suggested a link between advanced parental age and an increased risk of diseases in the offspring. Also, poor reproductive outcome has been described in pregnancies conceived by aged parents. Similarly, animal studies showed that aging negatively affects gametes, early embryonic development, pregnancy progression, and the postnatal phenotype of resulting offspring. However, how and to what extent parental age is a risk factor for the health of future generations is still a subject of debate. Notwithstanding the limitation of an animal model, the mouse model represents a useful tool to understand not only the influence of parental age on offspring phenotype but also the biological mechanisms underlying the poor reproductive outcome and the occurrence of diseases in the descendants. The present review aims at i) providing an overview of the current knowledge from mouse model about the risks associated with conception at advanced age (e.g. neurodevelopmental and metabolic disorders), ii) highlighting the candidate biological mechanisms underlying this phenomenon, and iii) discussing on how murine-derived data can be relevant to humans.
由于各种社会经济因素，全球范围内的晚育现象不断增加。在过去的十年中，越来越多的流行病学研究表明，高龄生育与后代患病风险之间存在关联。此外，高龄父母生育的妊娠结果也较差。同样，动物研究表明，衰老会对配子、早期胚胎发育、妊娠进展以及后代的出生后表型产生负面影响。然而，父母年龄是如何以及在多大程度上成为影响后代健康的风险因素，仍然是一个有争议的问题。尽管动物模型存在局限性，但小鼠模型是一种有用的工具，不仅可以了解父母年龄对后代表型的影响，还可以了解生殖结局不良和后代疾病发生的潜在生物学机制。本文综述的目的是：i）概述来自小鼠模型的关于高龄受孕相关风险的现有知识（例如神经发育和代谢紊乱），ii）强调该现象背后的候选生物学机制，以及 iii）讨论如何将源自鼠类的研究数据应用于人类。
