Guangdong Provincial Key Laboratory of Bioengineering Medicine, Department of Cell Biology, Jinan University, Guangzhou 510632, China.
Institute of Life Sciences, Wenzhou University, Wenzhou 325035, China.
Asian J Androl. 2022 Jul-Aug;24(4):335-344. doi: 10.4103/aja202193.
Testosterone production by Leydig cells (LCs) plays a crucial role in male reproduction. The functional degeneration of LCs can cause testosterone deficiency, ultimately resulting in primary male hypogonadism. Transplantation of exogenous LCs with the ability to produce testosterone in response to the regulation of the hypothalamus-pituitary-gonad axis could be a promising alternative option to treat male primary hypogonadism. Recent studies have shown that it is possible to generate Leydig-like cells from stem cells by various approaches. In addition, somatic cells, such as embryonic or adult fibroblasts, have also been successfully reprogrammed into Leydig-like cells. In this review, we summarized the recent advances in the generation of Leydig-like cells, with an emphasis on comparing the effectiveness and safety of different protocols used and the cells generated. By further analyzing the characteristics of Leydig-like cells generated from fibroblasts based on small signaling molecules and regulatory factors, we found that although the cells may produce testosterone, they are significantly different from real LCs. For future in vivo applications, it is important that the steroidogenic cells generated be evaluated not only for their steroidogenic functions but also for their overall cell metabolic state by proteomics or transcriptomic tools.
睾丸间质细胞（LCs）产生的睾酮在男性生殖中起着至关重要的作用。LCs 的功能退化可导致睾酮缺乏，最终导致原发性男性性腺功能减退症。移植具有在下丘脑-垂体-性腺轴的调节下产生睾酮能力的外源性 LCs，可能是治疗男性原发性性腺功能减退症的一种有前途的替代选择。最近的研究表明，通过各种方法可以从干细胞中产生类间质细胞。此外，胚胎或成体成纤维细胞等体细胞也已成功地被重编程为类间质细胞。在这篇综述中，我们总结了类间质细胞生成的最新进展，重点比较了不同方案的有效性和安全性以及所产生的细胞。通过进一步分析基于小分子信号分子和调节因子的成纤维细胞产生的类间质细胞的特征，我们发现，虽然这些细胞可能产生睾酮，但它们与真正的 LCs 有显著差异。对于未来的体内应用，重要的是不仅要通过蛋白质组学或转录组学工具评估所产生的类固醇生成细胞的类固醇生成功能，还要评估其整体细胞代谢状态。
