Gottlieb Bruce, Lombroso Rose, Beitel Lenore K, Trifiro Mark A
Lady Davis Institute for Medical Research, Sir Mortimer B Davis Jewish General Hospital, Department of Human Genetics, McGill University, Montreal, Canada. bruce.gottlieb@.mcgill.ca
Reprod Biomed Online. 2005 Jan;10(1):42-8. doi: 10.1016/s1472-6483(10)60802-4.
Idiopathic male infertility, accounting for 40% of all male infertility cases, is postulated to have a genetic basis. The androgen receptor (AR) plays a crucial post-meiotic role during male germ cell differentiation, which includes terminal differentiation of spermatids and their release from the seminiferous epithelium. Mutations in the AR gene result in a condition known as androgen insensitivity syndrome (AIS) affecting normal male morphogenesis. Depending on the severity of the syndrome, the external phenotype can range from normal female to normal male. In almost all cases affected individuals are infertile. In seven reported cases individuals appeared to suffer primarily or solely from male infertility, suggesting these AR mutations specifically cause male infertility. Three of these mutations are possibly population specific. Longer CAG repeats present in exon 1 of the AR have been studied as a possible risk factor for male infertility. Results are contradictory, with a trend to significance (Asian populations) and non-significance (European populations). Recent advances in protein modelling techniques may result in a much better understanding of the mechanism of action of the known infertility mutations. The determination of the significance of longer CAG repeats is likely to require studies that examine CAG repeat lengths in spermatozoa as well as patients' blood.
特发性男性不育症占所有男性不育病例的40%，据推测具有遗传基础。雄激素受体（AR）在男性生殖细胞分化过程中起着关键的减数分裂后作用，这包括精子细胞的终末分化及其从生精上皮的释放。AR基因的突变会导致一种称为雄激素不敏感综合征（AIS）的疾病，影响正常男性形态发生。根据该综合征的严重程度，外部表型可从正常女性到正常男性不等。几乎在所有受影响的病例中，个体均不育。在七例报告的病例中，个体似乎主要或仅患有男性不育症，提示这些AR突变特异性地导致男性不育。其中三个突变可能具有人群特异性。AR外显子1中存在的较长CAG重复序列已被研究作为男性不育的一个可能危险因素。结果相互矛盾，有显著趋势（亚洲人群）和无显著趋势（欧洲人群）。蛋白质建模技术的最新进展可能会使人们更好地理解已知不育突变的作用机制。确定较长CAG重复序列的意义可能需要在精子以及患者血液中检测CAG重复长度的研究。
