摘要：SummaryIn adult males, spermatogonia maintain lifelong spermatozoa production for oocyte fertilization. To understand spermatogonial metabolism we compared gene profiles in rat spermatogonia to publicly available mouse, monkey, and human spermatogonial gene profiles. Interestingly, rat spermatogonia expressed metabolic control factorsFoxa1,Foxa2, andFoxa3.Germline Foxa2 was enriched in Gfra1Hiand Gfra1Lowundifferentiated A-single spermatogonia. Foxa2-bound loci in spermatogonial chromatin were overrepresented by conserved stemness genes (Dusp6, Gfra1, Etv5, Rest, Nanos2, Foxp1) that intersect bioinformatically with conserved glutathione/pentose phosphate metabolism genes (Tkt, Gss, Gclc, Gclm, Gpx1, Gpx4, Fth), marking elevated spermatogonial GSH:GSSG. Cystine-uptake and intracellular conversion to cysteine typically couple glutathione biosynthesis to pentose phosphate metabolism. Rat spermatogonia, curiously, displayed poor germline stem cell viability in cystine-containing media, and, like primate spermatogonia, exhibited reduced transsulfuration pathway markers. Exogenous cysteine, cysteine-like mercaptans, somatic testis cells, and ferroptosis inhibitors counteracted the cysteine-starvation-induced spermatogonial death and stimulated spermatogonial growth factor activityin vitro.Graphical AbstractDisplay OmittedHighlights•Foxa2-bound loci are enriched with spermatogonial stemness genes in the rat germline•Spermatogonial stemness genes couple to glutathione/pentose phosphate pathways•Mammalian spermatogonia are deficient in transsulfuration pathway gene products•Cysteine-like factors counteract spermatogonial ferroptosis in soma-depleted culturesBiological Sciences; Developmental Biology; Systems Biology
