Wang Hongyu, Liu Xiaojun, Dong Shijue, Zhou Yang, Yu Jingyan, Zou Meng, Ding Mengqian, Kang Aiwen, Ji Nanxi, Zeng Xuhui, Zhang Xiaoning
Institute of Reproductive Medicine, Medical School, Nantong University, Nantong 226019, China.
Jiangsu Province Key Laboratory in University for Inflammation and Molecular Drug Target, Nantong University, Nantong 226019, China.
Int J Mol Sci. 2025 Jun 17;26(12):5801. doi: 10.3390/ijms26125801.
Long non-coding (lnc) RNAs exhibit tissue-specific expression characteristics and have been shown to be involved in the regulation of various biological processes. The testis is one of the organs with the most abundant lncRNAs. However, the functions of many testis-specific or -enriched lncRNAs in male fertility remain undisclosed. In this study, we screened lncRNA () to investigate its roles in spermatogenesis and male fertility using knockout (KO) mice. We found that mainly acted as an intact lncRNA rather than a small protein, being highly expressed in various spermatogenic cells, which suggests its potential involvement in spermatogenesis. Unexpectedly, the deletion of did not impact spermatogenesis or sperm functions. Intriguingly, two-thirds of the male KO were infertile, which was ascribed to the lack of sexual behaviors rather than abnormalities in spermatogenesis or sperm functions. Further results reveal that, compared with wild-type mice, free testosterone content in serum was significantly reduced in the KO infertile (KO-I) mice, whereas it was remarkably elevated in the testes. Correspondingly, , a key gene that promotes testosterone synthesis, was dramatically upregulated. and which are responsible for testosterone metabolism, were downregulated in the testes. In addition, the expression of sex hormone-binding globulin was observably elevated in the testes of KO-I mice, which might partially explain the decrease in testosterone in the serum. These results suggest that disruptions in testosterone synthesis and metabolism might contribute to the loss of libido in KO-I mice. Our findings expand the understanding of lncRNA function and provide novel insights into the role of lncRNAs in male fertility, particularly in relation to hormonal turnover disorders that mediate sexual behavior defects.
长链非编码（lnc）RNA具有组织特异性表达特征，并已被证明参与多种生物学过程的调控。睾丸是lncRNA最为丰富的器官之一。然而，许多睾丸特异性或富集的lncRNA在雄性生育中的功能仍未明确。在本研究中，我们筛选了lncRNA（），利用基因敲除（KO）小鼠研究其在精子发生和雄性生育中的作用。我们发现，主要作为完整的lncRNA而非小蛋白发挥作用，在各种生精细胞中高表达，这表明其可能参与精子发生。出乎意料的是，的缺失并未影响精子发生或精子功能。有趣的是，三分之二的雄性KO小鼠不育，这归因于性行为的缺乏，而非精子发生或精子功能异常。进一步的结果显示，与野生型小鼠相比，KO不育（KO-I）小鼠血清中的游离睾酮含量显著降低，而在睾丸中则显著升高。相应地，促进睾酮合成的关键基因显著上调。负责睾酮代谢的和在睾丸中下调。此外，KO-I小鼠睾丸中性激素结合球蛋白的表达明显升高，这可能部分解释了血清中睾酮的降低。这些结果表明，睾酮合成和代谢的紊乱可能导致KO-I小鼠性欲丧失。我们的发现扩展了对lncRNA功能的理解，并为lncRNA在雄性生育中的作用提供了新的见解，特别是与介导性行为缺陷的激素周转紊乱有关。
