不孕症引起了全球关注，睾酮紊乱是男性不孕症的常见原因。探索睾酮生物合成的关键因素可能为疾病研究和临床治疗提供新的见解。最近对三趾鼻骨综合征-1（Trps1）基因的研究集中在癌症方面；目前还不清楚Trps1在男性生殖系统中是否产生显著效应。本研究利用小鼠睾丸中三趾鼻骨综合征-1（Trps1）基因的单细胞RNA测序分析和靶向和荧光标记和RNA测序方法，研究了Trps1在小鼠睾丸间质细胞中的功能。通过腺相关病毒传递和条件性基因敲除模型，敲低Trps1在体外和体内均增加了睾酮的合成。结果显示，Trps1在睾丸间质细胞中的表达丰富。在Trps1缺陷后，睾酮合成因子-1（Sf-1）和类固醇合酶（Cyp11a1、Hsd3b、Cyp17a1和Hsd17b3）的表达水平以及睾酮分泌量均增加了。此外，Trps1缺陷降低了组蛋白去乙酰化酶1/2活性，增加了Sf-1启动子中组蛋白H3的乙酰化，从而促进了睾酮的分泌。有趣的是，Sf-1还通过激活转录因子2调节Trps1的转录。这些结果表明Trps1通过组蛋白乙酰化作用靶向Sf-1，影响类固醇激素合成，在小鼠睾丸间质细胞中发挥了关键作用。© 2023年。作者，独家许可给Springer Nature B.V.

Infertility has attracted global concern, and disruption of testosterone is a common cause of male infertility. Exploring the critical factors in testosterone biosynthesis may provide new insights for disease research and clinical therapy. Research on trichorhinophalangeal syndrome-1 (Trps1) gene has recently been focus on cancers; it is yet unknown whether Trps1 produces a marked effect in the male reproductive system. In the current study, single-cell RNA sequencing analysis of trichorhinophalangeal syndrome-1 gene (Trps1) expression in mouse testes and cleavage under targets and tagmentation and RNA sequencing were utilized to investigate the functionality of Trps1 in mouse Leydig cells. Knockdown of Trps1 increased testosterone synthesis in vitro and vivo using adeno-associated viral delivery and conditional knockout models. The results showed that Trps1 was abundantly expressed in Leydig cells. The expression levels of both steroidogenic factor-1 (Sf-1) and steroidogenic enzymes (Cyp11a1, Hsd3b, Cyp17a1, and Hsd17b3) as well as testosterone secretion were increased after Trps1 deficiency in vivo and vitro. Furthermore, disruption of Trps1 reduced histone deacetylase 1/2 activity and increased histone H3 acetylation in the Sf-1 promoter, thereby promoting testosterone secretion. Interestingly, Sf-1 also regulated the transcription of Trps1 through activating transcription factor 2. These results indicate that Trps1 targets Sf-1 to affect steroidogenesis through histone acetylation and shed light on the critical role of Trps1 functioning in the mouse Leydig cells.© 2023. The Author(s), under exclusive licence to Springer Nature B.V.