Department of Urology, The First Affiliated Hospital of Jinan University, Guangzhou 510630, China.
Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou 510060, China.
Asian J Androl. 2020 Sep-Oct;22(5):493-499. doi: 10.4103/aja.aja_122_19.
Phosphoribosyl-pyrophosphate synthetase 2 (PRPS2) is a rate-limiting enzyme and plays an important role in purine and pyrimidine nucleotide synthesis. Recent studies report that PRPS2 is involved in male infertility. However, the role of PRPS2 in hypospermatogenesis is unknown. In this study, the relationship of PRPS2 with hypospermatogenesis and spermatogenic cell apoptosis was investigated. The results showed that PRPS2 depletion increased the number of apoptotic spermatogenic cells in vitro. PRPS2 was downregulated in a mouse model of hypospermatogenesis. When PRPS2 expression was knocked down in mouse testes, hypospermatogenesis and accelerated apoptosis of spermatogenic cells were noted. E2F transcription factor 1 (E2F1) was confirmed as the target gene of PRPS2 and played a key role in cell apoptosis by regulating the P53/Bcl-xl/Bcl-2/Caspase 6/Caspase 9 apoptosis pathway. Therefore, these data indicate that PRPS2 depletion contributes to the apoptosis of spermatogenic cells and is associated with hypospermatogenesis, which may be helpful for the diagnosis of male infertility.
磷酸核糖焦磷酸合成酶 2（PRPS2）是一种限速酶，在嘌呤和嘧啶核苷酸合成中发挥重要作用。最近的研究报告称，PRPS2 与男性不育有关。然而，PRPS2 在精子发生减少症中的作用尚不清楚。在这项研究中，研究了 PRPS2 与精子发生减少症和生精细胞凋亡的关系。结果表明，PRPS2 耗竭增加了体外生精细胞的凋亡数量。PRPS2 在精子发生减少症的小鼠模型中下调。当 PRPS2 在小鼠睾丸中表达被敲低时，观察到精子发生减少症和生精细胞加速凋亡。E2F 转录因子 1（E2F1）被确认为 PRPS2 的靶基因，并通过调节 P53/Bcl-xl/Bcl-2/Caspase 6/Caspase 9 凋亡途径在细胞凋亡中发挥关键作用。因此，这些数据表明 PRPS2 耗竭导致生精细胞凋亡，并与精子发生减少症相关，这可能有助于男性不育症的诊断。
