Male Infertility and Single-Nucleotide Polymorphisms in the Testis-Specific Succinyl CoA: 3-Oxoacid CoA Transferase (SCOT-T/OXCT2 ) gene in a Japanese Cohort

Abstract Some cases of male infertility show an association with various genetic factors. However, putative causative genes remain inconclusive in the majority of cases and do not explain all types of male infertility. Succinyl CoA: 3-oxoacid CoA transferase (SCOT; EC 2.8.3.5) is a key enzyme for the metabolism of ketone bodies, and its testicular isotype (SCOT-T/OXCT2) is localized exclusively in the cytoplasm of spermatids and the midpiece of ejaculated sperm where mitochondria exist. SCOT-T has been suggested to play important roles in spermiogenesis and sperm function. This study compared the genomic DNA sequence of human SCOT-T in sterile males and proven-fertile control volunteers. We found four single nucleotide polymorphisms (SNPs): one in the 3′ noncoding region, and three in the coding region causing predicted amino acid substitutions. The prevalence of homozygous SNPs causing amino acid changes was significantly higher in infertile patients than in fertile controls. This study suggests that these SNPs have detrimental effects on SCOT-T enzyme activity, which influences male infertility