Castro-Nallar Eduardo, Bacallao Ketty, Parada-Bustamante Alexis, Lardone María C, López Patricia V, Madariaga Marcia, Valdevenito Raúl, Piottante Antonio, Ebensperger Mauricio, Castro Andrea
Institute of Maternal and Child Research, School of Medicine, University of Chile, Santa Rosa 1234, Santiago, Chile.
J Androl. 2010 Nov-Dec;31(6):552-9. doi: 10.2164/jandrol.109.008821. Epub 2010 Apr 8.
There is ample documentation supporting the fact that androgens are required for normal spermatogenesis. A minority of infertile men have abnormal testosterone blood levels or mild androgen receptor mutations. We investigated the androgen receptor CAG and GGN repeat lengths in Chilean men with spermatogenic impairment. We studied 117 secretory azoospermic/oligozoospermic men (93 idiopathic and 24 excryptorchidic), without Y-chromosome microdeletions, and 121 controls with normal spermatogenesis (42 obstructive and 79 normozoospermic men). Peripheral blood was drawn to obtain genomic DNA for polymerase chain reaction and automated sequencing of CAG and GGN repeats. Testicular characterization included hormonal studies, physical evaluation, and seminal and biopsy analysis. The CAG and GGN polymorphism distributions were similar among idiopathic men, excryptorchidic men, and controls and among the different types of spermatogenic impairment. However, the proportion of the CAG 21 allele was significantly increased in idiopathic cases compared to controls (P = .012 by Bonferroni test, odds ratio = 2.99, 95% confidence interval, 1.27-7.0) and the CAG 32 allele only was observed in excryptorchidic patients (P < .0002, Bonferroni test). Idiopathic cases with Sertoli cell-only syndrome showed the highest proportion of the CAG 21 allele (P = .024, χ(2) test). On the other hand, in idiopathic cases and controls the most common GGN allele was 23, followed by 24, but an inverse relation was found among excryptorchidic cases. The joint distribution of CAG and GGN in control, idiopathic, and excryptorchidic groups did not show an association between the 2 allele repeat polymorphisms (P > 0.05, χ(2) test). Our results suggest that the CAG 21 allele seems to increase the risk of idiopathic Sertoli cell-only syndrome. Moreover, the GGN 24 allele could be contributing to deranged androgen receptor function, associated with cryptorchidism and spermatogenic failure.
有大量文献支持雄激素是正常精子发生所必需的这一事实。少数不育男性的睾酮血液水平异常或存在轻度雄激素受体突变。我们研究了智利患有生精障碍男性的雄激素受体CAG和GGN重复长度。我们研究了117例分泌性无精子症/少精子症男性（93例特发性和24例隐睾症患者），这些患者无Y染色体微缺失，以及121例精子发生正常的对照者（42例梗阻性和79例正常精子症男性）。采集外周血以获取基因组DNA，用于CAG和GGN重复序列的聚合酶链反应和自动测序。睾丸特征分析包括激素研究、体格评估以及精液和活检分析。CAG和GGN多态性分布在特发性男性、隐睾症男性和对照者之间以及不同类型的生精障碍患者中相似。然而，与对照者相比，特发性病例中CAG 21等位基因的比例显著增加（经Bonferroni检验，P = 0.012，优势比 = 2.99，95%置信区间，1.27 - 7.0），并且仅在隐睾症患者中观察到CAG 32等位基因（P < 0.0002，Bonferroni检验）。仅支持细胞综合征的特发性病例显示CAG 21等位基因的比例最高（P = 0.024，χ²检验）。另一方面，在特发性病例和对照者中，最常见的GGN等位基因是23，其次是24，但在隐睾症病例中发现了相反的关系。CAG和GGN在对照、特发性和隐睾症组中的联合分布未显示这两个等位基因重复多态性之间存在关联（P > 0.05，χ²检验）。我们的结果表明，CAG 21等位基因似乎增加了特发性仅支持细胞综合征的风险。此外，GGN 24等位基因可能导致雄激素受体功能紊乱，这与隐睾症和生精失败有关。
