Sertoli cell only (SCO) syndrome is the predominant histology for men with non-obstructive azoospermia (NOA) and is usually of unexplained aetiology. Studies in mouse models indicated that the X-linked gene glucocorticoid-induced leucine zipper (GILZ) is essential for survival and differentiation of spermatogonia, and meiosis. GILZ deficiency results in a rapid and progressive loss of germ cells with SCO tubules and sterility in adults. The role of GILZ in human fertility has not been examined. Here we show that GILZ is localized to spermatogonia and spermatocytes in the human testis in a pattern analogous to that seen in mice. To assess the potential for an association between GILZ variants and human infertility, we sequenced the entire protein-coding regions of the GILZ gene in 65 SCO and 87 fertile Australian men. We identified six genetic variants, three of which had not been reported previously. Three variants, 107018665 G>A, 107018485 C>G and 106959283 C>T, were found at a low frequency only in SCO men. Although none of the identified variants changed the protein code, sequence analysis indicated that two variants, 107018665 G>A and 107018485 C>G, would completely abolish the exonic splicing enhancer (ESE)-binding motifs for the splicing factors SF2/ASF and SC35 respectively. This result prompted an assessment of whether these two variants were associated with male infertility in a separate population of men. We used a PCR-based SNP detection approach to screen an additional 52 NOA and 153 fertile Australian men, and 86 SCO and 54 fertile American men. None of these men carried either of these two variants. The cumulative allelic frequency of these variants is less than 1% in SCO men and no association with fertility status was observed. Our study suggests that GILZ variants are not common causes of SCO and NOA in Australian or American men.
© 2013 American Society of Andrology and European Academy of Andrology.