Gut microbiota induces dysspermatogenesis via microbial-derived phenylacetylglycine in Ggt1-deficient mice

Ggt1 deletion-induced gut microbiota dysbiosis disrupts spermatogenesis via β2AR-STAT3-SOCS3-STAT5B-Klk1bs signaling pathway. Specifically, PAGly-induced β2AR activation promotes STAT3 phosphorylation, which induces SOCS3 to suppress p-STAT5B dependent Klk1bs transcription. This mechanism underscores the critical role of gut-derived metabolites in regulating testicular function and identifies potential targets for microbiota-modulated male infertility. Video Abstract.