Infertility affects about 15% of heterosexual couples and male factors account for ~45–50% of clinical cases. Genetic factors play an important role in male infertility and thus we try to develop a cost-effective method for screening the genetic factors in male infertility. In our retrospective proof-of-concept study, we employed the high-throughput ligation-dependent probe amplification (HLPA) to examine the copy number by 115 genomic loci covering the Y chromosome, and 5 loci covering the X chromosome-specific region. We identified 8 sex chromosome aneuploid people from the low sperm concentration (LSC) group, and Y chromosome-specific microdeletion/duplications in 211 samples from the LSC group, and in 212 samples from the control group. 35 samples showed complete loss of AZFc (BPY2 to CDY1B deletion), which was not observed in controls. Nevertheless, a partial loss of AZFc (BPY2 to BPY2B deletion) was detected at comparable frequencies in both groups (68/211 vs. 108/212, respectively). And we further found structural variations in 28.6 and 26.9% samples from infertility and fertility groups. Moreover, we found that there were lower copy numbers for heterochromatic sequences in men with LSC. Especially, we reported that ultra-low relative copy number (RCN) (<0.5) type and low RCN (0.5 to <0.75) type in Yq12 were more often in the LSC group for the first time. Our results not only shed light on the potential role of low RCN in Yq12 in male infertility but also showed that HLPA can be a powerful and cost-effective tool for clinical screening in male infertility.

不育症影响约 15% 的异性恋夫妇，男性因素约占临床病例的 45-50%。遗传因素在男性不育症中起重要作用，因此我们试图开发一种具有成本效益的方法来筛查男性不育症中的遗传因素。在我们的回顾性概念验证研究中，我们采用高通量连接依赖性探针扩增 (HLPA) 来检查覆盖 Y 染色体的 115 个基因组基因座和覆盖 X 染色体特定区域的 5 个基因座的拷贝数。我们从低精子浓度 (LSC) 组中确定了 8 名性染色体非整倍体人群，在 LSC 组的 211 份样本和对照组的 212 份样本中发现了 Y 染色体特异性微缺失/重复。35 个样本显示 AZFc 完全丢失（BPY2到CDY1B删除），这在对照中未观察到。然而，在两组中以相当的频率检测到 AZFc 的部分丢失（BPY2到BPY2B缺失）（分别为 68/211 对 108/212）。我们进一步发现了来自不育和生育组的 28.6% 和 26.9% 样本的结构变异。此外，我们发现患有 LSC 的男性异染色质序列的拷贝数较低。特别是，我们首次报道了 Yq12 中的超低相对拷贝数（RCN）（​​<0.5）型和低 RCN（0.5 至 <0.75）型在 LSC 组中更常见。我们的研究结果不仅揭示了 Yq12 中低 RCN 在男性不育症中的潜在作用，而且表明 HLPA 可以成为男性不育症临床筛查的强大且具有成本效益的工具。