GGN1 in the testis and ovary and its variance within the Australian fertile and infertile male population

Mouse gametogenetin (Ggn) is a testis-enriched gene that encodes multiple spliced transcripts giving rise to three predicted protein isoforms: GGN1, GGN2 and GGN3. Of these, GGN1 has been linked to germ cell development. Based on the spatial and temporal expression pattern of GGN1 during mouse spermatogenesis, it has been proposed as a candidate human infertility gene. Here, we report the localization of GGN1 in the human testis and ovary compared with the mouse orthologue. Within the testis, GGN1 was confined to pachytene spermatocytes and spermatids. During mid-prophase GGN1 redistributes from a solely cytoplasmic localization to both cytoplasmic and nuclear in late prophase spermatocytes and round spermatids, and is ultimately incorporated into the sperm tail. Within both mouse and human ovaries, GGN1 was localized within granulosa cells. Lower levels of expression were observed in mouse oocytes and the cumulus cells. Furthermore, to define the level of sequence variation in the fertile population and to assess the potential for an association with male infertility, we sequenced the coding region of human GGN in 100 idiopathic oligospermic infertile and 100 control men. Fifteen genetic variants were identified, of which 10 had not previously been reported. No significant associations with fertility status were observed, suggesting that variance in the GGN gene are not a common cause of oligospermic infertility in Australian men.