Aberrant expression of TAR DNA binding protein-43 is associated with spermatogenic disorders in men

Loss of function of TAR DNA-binding protein (TDP-43) has been implicated in neurodegenerative disorders inbothhumansandanimalmodels.TDP-43hasalsobeenshowntobecis-actingtranscriptionalrepressoroftheacrosome vesicle (Acrv) gene in mice. In the present study, we investigated the expression of the TDP-43 transcript (TARDBP) and protein in germ cells from 11 fertile and 98 subfertile men to verify its potential association with poor seminograms. The expression profile of TDP-43 was characterised in immature germ cells and spermatozoa from semen from fertile and subfertile men using reverse transcription-polymerase chain reaction, western blotting and immunofluorescence. Although germ cells from subfertile men tested negative for TARDBP, the full-length message of the same was detected infertilemen.TDP-43wasdetectedinspermatozoafromfertilemenusingwesternblotanalysisandimmunofluorescence. The expression of this protein was negligible in spermatozoa from men with primary spermatogenic dysfunction. We concludethat adeficiencyintheTDP-43expressionis associatedwith defectivespermatogenesis andmaleinfertility. We propose that TDP-43 could be used as a marker of male factor infertility.