Identification of novel polymorphisms in the nuclear protein genes and their relationship with human sperm protamine deficiency and severe male infertility

Objective: To screen populations of fertile men, severely infertile men, and infertility patients with aberrations in the protamine-1-to-protamine-2 ratio (P1/P2) for clinically relevant alterations in the P1, P2, transition protein 1 (TP1), and transition protein 2 (TP2) genes. Design: Prospective case-control study. Setting: University-based infertility clinic. Patient(s): Ninety-six fertile men, 96 severely infertile men, and 96 infertility patients with aberrations in the sperm, P1/P2 ratio. Intervention(s): Sperm nuclear protein extraction, gel electrophoresis, and densitometry to evaluate the P1/P2 ratios of infertility patients. DNA extraction, polymerase chain reaction (PCR), and gene sequencing to screen the nuclear protein genes. Main Outcome Measure(s): Sperm P1/P2 ratios and single nucleotide polymorphisms (SNPs) in the sperm nuclear protein genes (P1, P2, TP1, and TP2). Result(s): Fifteen SNPs were identified in the nuclear protein genes, 12 of which were previously unreported. Five variants were identified that resulted in amino acid changes (one in P1, one in TP1, and three in TP2). The frequency of the 15 SNPs was similar in protamine-deficient patients, severely infertile patients, and fertile controls. Conclusion(s): A number of SNPs are present in the testis-specific nuclear protein genes. However, the gene variants do not appear to underlie protamine deficiency and severe male infertility.