Wang Lei, Sun Juan, Han Jin, Ma Zhaowen, Pan Meiling, Du Zhaojin
Reproductive Medical Center, Zaozhuang Maternal and Child Health Hospital, Zaozhuang, China.
Department of Gynaecology, Zaozhuang Maternal and Child Health Hospital, Zaozhuang, China.
Int J Stem Cells. 2021 Aug 30;14(3):341-350. doi: 10.15283/ijsc21001.
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. 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.
全球约15%的夫妇患有不孕症，男性因素导致的不育病例约占总不育病例的30%。然而，由于对潜在机制的认识模糊，治疗进展甚微。最近，微小RNA已成为精子发生过程中的关键因素。对小鼠睾丸和精母细胞培养系统进行了miR-181a的表达谱分析。采用细胞和生化分析方法检测miR-181a的作用，鉴定其靶标S6K1，并使用S6K1化学抑制剂阐明其功能。通过对人类睾丸样本的分析来验证研究结果。在小鼠精子发生过程中，miR-181a水平上调，敲低miR-181a可减弱细胞增殖和G1/S期阻滞，并增加S6K1的水平，而S6K1被确定为miR-181a的下游靶标。S6K1的过表达也导致精母细胞生长停滞，而S6K1抑制剂可挽救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，miR-181a水平低与精子发生过程中的缺陷相关。miR-181a被确定为一种新的调节因子，高水平的miR-181a通过靶向S6K1促进精子发生。
