抄録
Approximately 10% of couples attempting to conceive over a period of 2 year are unable to become pregnant and 20% of those cases are attributable to a male factor alone. Testicular sperm extraction (TESE) with ICSI (TESE-ICSI) is becoming the first-line treatment for male infertility, especially for azoospermia (non obstructive azoospermia: NOA or obstructive azoospermia: OA) . Recently, the sperm retrieval rate (SRR) by microdissection TESE was reported to be approximately 45% and higher than by conventional TESE. However, still more than 50% of NOA cases are unable to obtain testicular sperm and even if they get testicular sperm, the fertilization rate, clinical implantation rate and clinical pregnancy rate were not enough high and lower in the NOA compared with the OA. Thus further breakthrough is required for higher SRR and subsequent high clinical pregnancy rate. To gain insight into the genetic factors implicated in male infertility, we have studied single nucleotide polymorphisms of the various spermiogenic genes in human male. Protamines, which are the major DNA-binding proteins in the sperm nucleus, package the DNA into the sperm head. Analysis of the human protamine-1 (PRM1) and -2 (PRM2) gene sequences in 226 sterile male patients and in 270 proven-fertile male volunteers revealed four single nucleotide polymorphisms (SNPs) in the PRM1 coding region, which did not cause any amino acid substitutions, and one SNP in the PRM2 gene, which produced translation termination. We also observed one SNP in the 3' non-coding region of the PRM1 gene, and two SNPs within the intron of the PRM2 gene. The prevalence of these SNPs was similar in both infertile patients and in proven-fertile volunteers, except that the c248t alteration in the PRM2 gene induced a nonsense colon under conditions of heterozygosity in one infertile patient. Although the PRM1 and PRM2 genes are highly conserved, the single SNP in the PRM2 gene that induces translation termination may result in male infertility due to haploinsufficiency of PRM2. Further investigation of spermiogenic genes will reveal novel causative genes for the different type of idiopathic male infertility.
