Association of a novel human mtDNA ATPase6 mutation with immature sperm cells

This study reports the first clearly defined heteroplasmic mutation in imma ture human sperm cells. The human sperm mitochondrial genome from residue 8 186-9341 was analysed with the aim of identifying point mutations which may be associated with human male infertility. The semen samples analysed were obtained from 88 fertile men, 19 with oligozoospermia, and 12 with severe oligozoospermia. Using single strand conformation polymorphism analysis a h eteroplasmic T to C transition was detected in the ATPase6 gene, at nucleot ide position 8821, in semen samples from one out of 12 (8%) severely oligoz oospermic men, but not in oligozoospermic men or normospermic men. This mut ation changed the amino acid serine to proline at residue 99 of the mitocho ndrial ATPase6 in a region which is highly conserved in other vertebrates i ncluding rat, bovine, chicken, salmonids and Xenopus. The mutation was dete cted in semen samples collected from the same man 9 months apart and in per ipheral blood lymphocytes. Single sperm cell analyses did not find this mut ation in the mature sperm, but the mutation was detected in 7% of immature spermatids. Our finding suggests that immature spermatids with this mutatio n fail to develop fully.