Abstract
Prdx6 (-/-) male mice are subfertile, and the deficiency or inactivation of Peroxiredoxins (PRDXs) is associated with human male infertility. We elucidate the impact of the lack of PRDX6 or inhibition of its calcium-independent phospholipase A(2) (Ca(2+)-iPLA(2)) activity by MJ33 on fertilization competence of mouse spermatozoa. Sperm motility, viability, fertilization and blastocyst rates were lower in Prdx6 (-/-) spermatozoa than in C57BL/6J wild-type (WT) controls (p ≤ 0.05). MJ33 inhibited the PRDX6 Ca(2+)-iPLA(2) activity and reduced these parameters in WT spermatozoa compared with controls (p ≤ 0.05). Levels of lipid peroxidation and of superoxide anion (O(2)(•─)) were higher in Prdx6 (-/-) than in WT spermatozoa (p ≤ 0.05). MJ33 increased the levels of lipid peroxidation and mitochondrial O(2)(•─) production in treated versus non-treated WT spermatozoa. Acrosome reaction, binding to zona pellucida and fusion with the oolemma were lower in Prdx6 (-/-) capacitated spermatozoa than WT capacitated controls and lower in WT spermatozoa treated with the PRDX6 inhibitor. In conclusion, the inhibition of the PRDX6 Ca(2+)-iPLA(2) activity promotes an oxidative stress affecting viability, motility, and the ability of mouse spermatozoa to fertilize oocytes. Thus, PRDX6 has a critical role in the protection of the mouse spermatozoon against oxidative stress to assure fertilizing competence.