Single-cell transcriptome profiling implicates the psychological stress-induced disruption of spermatogenesis.

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.