Gut microbiota induces dysspermatogenesis via microbial-derived phenylacetylglycine (PRJCA042012)

This study demonstrates that male gamma-glutamyl transferase 1-deletion (Ggt1-/-) mice exhibits infertility phenotypes, including reduced germ and testicular Leydig cell numbers, increased rates of abnormal sperms, and altered reproductive hormone levels. Metabolomic analysis reveals elevated levels of the gut microbial-derived metabolite phenylacetylglycine (PAGly) in serum and testes of Ggt1-/- mice.In addition, integrated CUT&Tag and ATAC-Seq analyses reveal that transcription factor STAT5B occupies regulatory elements near Klk1b transcription start sites (TSS), confirming that transcription factor STAT5B directly regulates Klk1b gene transcription.