Kühnert Bianca, Nieschlag Eberhard
Institute of Reproductive Medicine of the University, Domagkstr. 11, D-48129 Muenster, Germany.
Hum Reprod Update. 2004 Jul-Aug;10(4):327-39. doi: 10.1093/humupd/dmh030. Epub 2004 Jun 10.
Delayed childbearing is a common phenomenon in industrialized countries. This review focuses on age-associated alterations of male fertility and genetic risks. Semen volume, sperm motility and sperm morphology decrease with age, whereas the data concerning sperm concentration are conflicting. The age-related changes of semen parameters reflect the histological modifications which are found to varying degrees in individual testes. Men aged >40 years contribute to reduced fertility and fecundity of a couple, especially when the female partner is also of advanced age. Because relatively few children are born to older fathers and genetic diseases are rare, there is little statistical power supporting an association of genetic diseases in the offspring with advancing paternal age. Nevertheless, autosomal dominant diseases and some diseases of complex aetiology, such as schizophrenia, are associated with advancing paternal age. The single point mutations in sperm which are responsible for achondroplasia and Apert's syndrome, two autosomal dominant diseases, increase with the man's age. In case of Apert's syndrome this increase is believed to be due to a pre-meiotic selection of mutant spermatogonia. Although structural chromosome anomalies and disomies of certain chromosomes increase in sperm with the man's age, paternal age is, with the exception of trisomy 21, not associated with numerical or de novo structural chromosomal aberrations in newborns. However, even if the genetic risk for progeny from older fathers is slightly increased, the risk to the individual is low.
晚育在工业化国家是一种常见现象。本综述聚焦于男性生育能力与年龄相关的变化以及遗传风险。精液量、精子活力和精子形态会随着年龄增长而下降,而关于精子浓度的数据则存在矛盾。精液参数的年龄相关变化反映了在个体睾丸中不同程度存在的组织学改变。40岁以上男性会导致夫妻生育力和生殖力下降,尤其是当女性伴侣年龄也较大时。由于年长父亲生育的孩子相对较少且遗传疾病罕见,因此几乎没有统计学证据支持后代遗传疾病与父亲年龄增长之间存在关联。然而,常染色体显性疾病以及一些病因复杂的疾病,如精神分裂症,与父亲年龄增长有关。导致两种常染色体显性疾病——软骨发育不全和阿佩尔综合征的精子单点突变会随着男性年龄增长而增加。就阿佩尔综合征而言,这种增加被认为是由于减数分裂前突变精原细胞的选择。尽管随着男性年龄增长,精子中的结构染色体异常和某些染色体的二体性会增加,但除了21三体综合征外,父亲年龄与新生儿的染色体数目或新发结构染色体畸变并无关联。然而,即使年长父亲的后代遗传风险略有增加,对个体而言风险仍然较低。