Aitken R John, Baker Mark A, Sawyer Dennis
ARC Centre of Excellence in Biotechnology and Development, Discipline of Biological Sciences, School of Environmental and Life Sciences, University of Newcastle, NSW 2308, Australia.
Reprod Biomed Online. 2003 Jul-Aug;7(1):65-70. doi: 10.1016/s1472-6483(10)61730-0.
The human male is characterized by extremely poor semen quality as reflected in the number, morphology and motility of the spermatozoa and a high incidence of nuclear and mitochondrial DNA damage. As a consequence of these factors, defective sperm function is thought to be a major contributor to the aetiology of human infertility, as well as childhood diseases including dominant genetic mutations such as achondroplasia and cancer. Factors associated with the origin of poor semen quality include: (i) a lack of selection pressure for high fecundity genes in developed countries, (ii) an evolutionary lineage associated with the deterioration of several male fertility genes in humans and their close ancestors, (iii) genetic factors including, but not limited to, Y-chromosome deletions (iv) paternal age and (v) environmental factors. A model is proposed whereby factors such as ageing or environmental toxicants initiate DNA strand breakage in the spermatozoa of affected males, eventually leading to a mutation in the embryo. This hypothesis stresses the importance of discovering the identity of those environmental factors that are capable of damaging DNA integrity in the male germ line. Such information could make an important contribution to understanding of the origins of both male infertility and a variety of pathological conditions that affect humans, including cancer and dominant genetic disease.
人类男性的特征是精液质量极差，这体现在精子的数量、形态和活力上，以及核DNA和线粒体DNA损伤的高发生率。由于这些因素，精子功能缺陷被认为是人类不育病因的主要因素，也是包括软骨发育不全等显性基因突变和癌症在内的儿童疾病的主要因素。与精液质量差的起源相关的因素包括：（i）发达国家对高生育力基因缺乏选择压力；（ii）与人类及其近亲中几个男性生育力基因退化相关的进化谱系；（iii）遗传因素，包括但不限于Y染色体缺失；（iv）父亲年龄；（v）环境因素。提出了一个模型，据此衰老或环境毒物等因素会引发受影响男性精子中的DNA链断裂，最终导致胚胎发生突变。这一假设强调了发现那些能够损害男性生殖系中DNA完整性的环境因素身份的重要性。这些信息对于理解男性不育以及包括癌症和显性遗传病在内的影响人类的各种病理状况的起源可能会做出重要贡献。
