Approximately 15% of couples suffer from infertility worldwide, and male factors contribute to about 30% of total sterility cases. However, there is little progress in treatments due to the obscured understanding of underlying mechanisms. Recently microRNAs have emerged as a key player in the process of spermatogenesis. Expression profiling of miR-181a was carried out in murine testes and spermatocyte culture system. In vitro cellular and biochemical assays were used to examine the effect of miR-181a and identify its target S6K1, as well as elucidate the function with chemical inhibitor of S6K1. Human testis samples analysis was employed to validate the findings. miR-181a level was upregulated during mouse spermatogenesis and knockdown of miR-181a attenuated the cell proliferation and G1/S arrest and increased the level of S6K1, which was identified as a downstream target of miR-181a. Overexpression of S6K1 also led to growth arrest of spermatocytes while inhibitor of S6K1 rescued the miR-181a knockdown-mediated cell proliferation defect. In human testis samples of azoospermia patients, low level of miR-181a was correlated with defects in the spermatogenic process. miR-181a is identified as a new regulator and high level of miR-181a contributes to spermatogenesis via targeting S6K1.

中文翻译：

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MiR-181a 通过靶向 S6K1 通路促进精子发生。

全世界大约有 15% 的夫妇患有不孕症，而男性因素导致了大约 30% 的不孕症病例。然而，由于对潜在机制的理解模糊，治疗方面进展甚微。最近，microRNA 已成为精子发生过程中的关键参与者。在鼠睾丸和精母细胞培养系统中进行了 miR-181a 的表达谱分析。体外细胞和生化分析用于检查 miR-181a 的作用并确定其靶标 S6K1，并阐明 S6K1 化学抑制剂的功能。人类睾丸样本分析被用来验证研究结果。miR-181a 水平在小鼠精子发生过程中上调，敲除 miR-181a 减弱细胞增殖和 G1/S 期阻滞，并增加 S6K1 的水平，S6K1 被鉴定为 miR-181a 的下游靶标。S6K1 的过表达也导致精母细胞的生长停滞，而 S6K1 的抑制剂挽救了 miR-181a 敲低介导的细胞增殖缺陷。在无精子症患者的人类睾丸样本中，低水平的 miR-181a 与生精过程中的缺陷相关。