Testosterone and follicle stimulating hormone (FSH)-dependent glyoxalase 1 up-regulation sustains the viability of porcine Sertoli cells through the control of hydroimidazolone (MG-H1)- and argpyrimidine-mediated NF-κB pathway.

As SCs play a central role in germ cesurvival, their death may results in marked germ cell loss and infertility (Eid et al., 2012; Oliveira et al., 2015). As SCs play a central role in germ cell survival, their death may result in marked germ cell loss and infertility (Eid et al., 2012; Oliveira et al., 2015). As SCs play a central role in germ cell survival, their death may result in marked germ cell loss and infertility (Eid et al., 2012; Oliveira et al., 2015). Sertoli cells (SCs) are the only somatic cells within the seminiferous tubules and are essential for regulating spermatogenesis. Factors that enhance or diminish the viability of SCs may have profound effects on spermatogenesis. Yet the mechanisms underlying the maintainance of SC viability remain largely unknown. Glyoxalase 1 (Glo1) serves to detoxify methylglyoxal (MG), a highly reactive carbonyl species mainly formed during glycolysis, which is a potent precursor of cytotoxic advanced glycation end products (AGEs). Hydroimidazolone (MG-H1) and argpyrimidine (ArgPyr) are AGEs resulting from MG-mediated post-translational modification of arginine residues in various proteins. The role of Glo1 and MG-derived AGEs in regulating the fate of SCs has never been investigated. By using gene silencing and the specific MG scavenger, aminoguanidine, we demonstrate that Glo1, under testosterone and follicle stimulating hormone control, sustains viability of porcine neonatal SCs through a mechanism involving the NF-κB pathway. Glo1 knock-down induces a mitochondrial apoptotic pathway driven by the intracellular accumulation of MG-H1 and ArgPyr that desensitizes NF-kB signaling by modifying the inhibitor of NF-κB kinase, IKKß. To the best of our knowledge, this is the first report describing a role for Glo1 and MG-derived AGEs in SC biology, providing valuable new insights into the potential involvement of this metabolic axis into spermatogenesis.