Department of Pharmacology and Therapeutics, McGill University, Montréal, QC, Canada.
Nat Rev Urol. 2013 Apr;10(4):227-34. doi: 10.1038/nrurol.2013.18. Epub 2013 Feb 26.
Several studies have demonstrated a decline in the male reproductive system, sperm quality, and fertility with advancing paternal age, yet many of the biological mechanisms that underlie this process remain poorly understood. It is unclear whether the problem arises from the progenitor spermatogonial stem cells (for example, from an accumulation of DNA damage and mutations), from the somatic niche present in the testis (consisting of Sertoli and peritubular myoid cells), or from a combination of the two. Current data, albeit from a small number of studies, suggest that both factors have a role in age-associated germ cell loss. What is clear, on the other hand, is that mounting evidence links paternal age to chromosomal damage and genetic problems in the children of older fathers. The frequency of de novo mutations increases markedly with age, leading to increased risk of breast cancer, cardiac defects, developmental disorders, behavioural disorders, and neurological disease in the children of older men. The current trend towards fathering children at a later age raises concerns regarding the risk of offspring developing complex multigene diseases.
多项研究表明，随着父亲年龄的增长，男性生殖系统、精子质量和生育能力会下降，但这一过程背后的许多生物学机制仍知之甚少。目前尚不清楚问题是源于祖原生殖细胞干细胞（例如，由于 DNA 损伤和突变的积累），还是源于睾丸中存在的体细胞生态位（由支持细胞和小管周肌样细胞组成），亦或是这两者的结合。尽管目前的数据来自少数几项研究，但这些数据表明，这两个因素都与与年龄相关的生殖细胞丧失有关。另一方面，越来越多的证据表明，父亲的年龄与年长父亲的孩子的染色体损伤和遗传问题有关。新突变的频率随着年龄的增长而显著增加，导致年长男性的孩子患乳腺癌、心脏缺陷、发育障碍、行为障碍和神经疾病的风险增加。目前晚育的趋势令人担忧，因为这会增加后代患上复杂的多基因疾病的风险。
