State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing, China.
PLoS One. 2013;8(1):e53443. doi: 10.1371/journal.pone.0053443. Epub 2013 Jan 8.
The meiotic program initiation pathway genes (CYP26B1, NANOS1 and STRA8) have been proposed to play key roles in spermatogenesis.
To elucidate the exact role of the genetic variants of the meiosis initiation genes in spermatogenesis, we genotyped the potential functional genetic variants of CYP26B1, NANOS1 and STRA8 genes, and evaluated their effects on spermatogenesis in our study population.
DESIGN, SETTING, AND PARTICIPANTS: In this study, all subjects were volunteers from the affiliated hospitals of Nanjing Medical University between March 2004 and July 2009 (NJMU Infertile Study). Total 719 idiopathic infertile cases were recruited and divided into three groups according to WHO semen parameters: 201 azoospermia patients (no sperm in the ejaculate even after centrifugation), 155 oligozoospermia patients (sperm counts <20×10(6)/ml) and 363 infertility/normozoospermia subjects (sperm counts >20×10(6)/ml). The control group consisted of 383 subjects with normal semen parameters, all of which had fathered at least one child without assisted reproductive technologies.
Eight single nucleotide polymorphisms (SNPs) in CYP26B1, NANOS1 and STRA8 genes were determined by TaqMan allelic discrimination assay in 719 idiopathic infertile men and 383 healthy controls.
The genetic variant rs10269148 of STRA8 gene showed higher risk of spermatogenic impairment in the groups of abnormospermia (including azoospermia subgroup and oligozoospermia subgroup) and azoospermia than the controls with odds ratios and 95% confidence intervals of 2.52 (1.29-4.94) and 2.92 (1.41-6.06), respectively (P = 0.006, 0.002 respective). Notably, larger sample size studies and in vivo or in vitro functional studies are needed to substantiate the biological roles of these variants.
Our results provided epidemiological evidence supporting the involvement of genetic polymorphisms of the meiotic program initiation genes in modifying the risk of azoospermia and oligozoospermia in a Han-Chinese population.
减数分裂起始途径基因（CYP26B1、NANOS1 和 STRA8）被认为在精子发生中发挥关键作用。
为了阐明起始基因的遗传变异在精子发生中的确切作用，我们对 CYP26B1、NANOS1 和 STRA8 基因的潜在功能遗传变异进行了基因分型，并在我们的研究人群中评估了它们对精子发生的影响。
设计、地点和参与者：在这项研究中，所有受试者均为 2004 年 3 月至 2009 年 7 月期间南京医科大学附属医院的志愿者（NJMU 不孕研究）。根据世界卫生组织精液参数，将 719 例特发性不育患者分为三组：201 例无精子症患者（即使离心后精液中也没有精子）、155 例少精子症患者（精子计数<20×10（6）/ml）和 363 例不育/正常精子症患者（精子计数>20×10（6）/ml）。对照组由 383 名精液参数正常的受试者组成，他们均未借助辅助生殖技术生育至少一个孩子。
采用 TaqMan 等位基因鉴别检测法测定 719 例特发性不育男性和 383 名健康对照者 CYP26B1、NANOS1 和 STRA8 基因中的 8 个单核苷酸多态性（SNP）。
STRA8 基因的遗传变异 rs10269148 在异常精子症（包括无精子症亚组和少精子症亚组）和无精子症组中与对照组相比，具有更高的生精损伤风险，比值比和 95%置信区间分别为 2.52（1.29-4.94）和 2.92（1.41-6.06）（P=0.006，0.002）。值得注意的是，需要更大的样本量研究和体内或体外功能研究来证实这些变异的生物学作用。
我们的研究结果提供了流行病学证据，支持减数分裂起始基因的遗传多态性参与了汉族人群无精子症和少精子症风险的改变。
