Male infertility has emerged as a global issue, partly attributed to psychological stress. However, the cellular and molecular mechanisms underlying the adverse effects of psychological stress on male reproductive function remain elusive. We created a psychologically stressed model using terrified-sound and profiled the testes from stressed and control rats using single-cell RNA sequencing. Comparative and comprehensive transcriptome analyses of 11,744 testicular cells depicted the cellular landscape of spermatogenesis and revealed significant molecular alterations of spermatogenesis suffering from psychological stress. At the cellular level, stressed rats exhibited delayed spermatogenesis at the spermatogonia and pachytene phases, resulting in reduced sperm production. Additionally, psychological stress rewired cellular interactions among germ cells, negatively impacting reproductive development. Molecularly, we observed the down-regulation of anti-oxidation-related genes and up-regulation of genes promoting reactive oxygen species (ROS) generation in the stress group. These alterations led to elevated ROS levels in testes, affecting the expression of key regulators such as ATF2 and STAR, which caused reproductive damage through apoptosis or inhibition of testosterone synthesis. Overall, our study aimed to uncover the cellular and molecular mechanisms by which psychological stress disrupts spermatogenesis, offering insights into the mechanisms of psychological stress-induced male infertility in other species and promises in potential therapeutic targets.

中文翻译：

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单细胞转录组分析表明心理压力引起的精子发生中断

男性不育已成为一个全球性问题，部分原因是心理压力。然而，心理压力对男性生殖功能产生不利影响的细胞和分子机制仍然难以捉摸。我们使用恐惧声音创建了一个心理应激模型，并使用单细胞 RNA 测序对应激大鼠和对照大鼠的睾丸进行了分析。对 11,744 个睾丸细胞的比较和综合转录组分析描绘了精子发生的细胞景观，并揭示了心理压力下精子发生的显着分子变化。在细胞水平上，应激大鼠在精原细胞和粗线期表现出精子发生延迟，导致精子产量减少。此外，心理压力重新连接了生殖细胞之间的细胞相互作用，对生殖发育产生负面影响。从分子角度来看，我们观察到应激组中抗氧化相关基因的下调和促进活性氧（ROS）产生的基因的上调。这些改变导致睾丸中 ROS 水平升高，影响 ATF2 和 STAR 等关键调节因子的表达，从而通过细胞凋亡或抑制睾酮合成造成生殖损伤。总体而言，我们的研究旨在揭示心理压力扰乱精子发生的细胞和分子机制，为其他物种中心理压力诱发男性不育的机制提供见解，并有望找到潜在的治疗靶点。