Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran.
Fertility and Infertility Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran.
J Gene Med. 2020 Apr;22(4):e3161. doi: 10.1002/jgm.3161. Epub 2020 Feb 7.
Autophagy affects various aspects of the male reproductive system. Any defects in this process may lead to azoospermia. However, the exact molecular mechanisms of the autophagy pathway have remained largely obscure. Therefore, the present study aimed to investigate levels of autophagy pathway gene expression (i.e. Lc3B, Beclin1, ATG5 and Bcl2) in azoospermic patients.
The levels of Lc3B, Beclin1, ATG5 and Bcl2 mRNA expression in azoospermic patients and fertile males were evaluated by a real-time polymerase chain reaction technique. In addition, diagnostic evaluation based on the receiver-operating characteristic (ROC) curve was performed.
The results obtained showed the decreased expression of Lc3B, Beclin1 and ATG5 genes in infertile patients compared to the control group (p < 0.05), whereas Bcl2 expression was increased in samples (p < 0.05). A diagnostic evaluation by ROC curve and calculation of the area under the curve showed that, using a cut-off relative quantification of 4.550, 0.052, 0.056 and 0.012, the sensitivity of Lc3B, Beclin1, ATG5 and Bcl2 genes was 87.5%, 93.8%, 93.8% and 90%, respectively. In addition, a specificity of 76.7%, 76.7%, 93.3% and 81.2%, respectively, was observed.
As a first study, the current research suggests that an alteration in the expression of autophagy pathway genes may be associated with male infertility. Based on our finding, the increased expression of Bcl2 and formation of Becline1/Bcl2 complex, which inhibits Beclin1 recruitment, may lead to a decrease of the autophagy process in azoospermic patients. Accordingly, upon further investigation, the autophagy could be considered as an important aspect during spermatogenesis.
自噬作用影响男性生殖系统的各个方面。该过程的任何缺陷都可能导致无精子症。然而，自噬途径的确切分子机制在很大程度上仍不清楚。因此，本研究旨在研究无精子症患者中自噬途径基因表达（即 Lc3B、Beclin1、ATG5 和 Bcl2）的水平。
采用实时聚合酶链反应技术评估无精子症患者和正常生育男性的 Lc3B、Beclin1、ATG5 和 Bcl2 mRNA 表达水平。此外，还进行了基于受试者工作特征（ROC）曲线的诊断评估。
结果显示，与对照组相比，不育患者的 Lc3B、Beclin1 和 ATG5 基因表达降低（p<0.05），而 Bcl2 表达升高（p<0.05）。ROC 曲线诊断评估和曲线下面积计算表明，使用相对定量 4.550、0.052、0.056 和 0.012 的截断值，Lc3B、Beclin1、ATG5 和 Bcl2 基因的灵敏度分别为 87.5%、93.8%、93.8%和 90%。此外，还观察到分别为 76.7%、76.7%、93.3%和 81.2%的特异性。
作为第一项研究，本研究表明自噬途径基因表达的改变可能与男性不育有关。根据我们的发现，Bcl2 的表达增加和 Becline1/Bcl2 复合物的形成，抑制了 Beclin1 的募集，可能导致无精子症患者自噬过程的减少。因此，进一步研究表明，自噬可能是精子发生过程中的一个重要方面。
