Endocrine Abstracts

Background: During spermatogenesis protamines replace histones in sperm head. Haploinsufficiency of the protamine (PRM) 1 or PRM2 gene causes infertility in mice. A mutation in PRM1 was associated with increased abnormal sperm morphology in infertile men¹. We assessed the frequency of mutations and SNPs in the PRM1 and PRM2 gene in infertile patiens with normal sperm concentration and reduced morphology, a phenotype similar to that of the Prm1 deficient knockout mice.

Material and Methods: Using the institutional database (Androbase^©) we identified 29 infertile men with normal sperm concentration and severe idiopathic teratozoospermia (<7% normal forms). PRM1 and PRM2 were sequenced in the patients and in 29 controls with normal spermatogenesis.

Results: Two single SNPs were identified in the PRM1 gene. One (A230C) was known (rs737008) as a synomynous polymorphism in exon 2 with a heterozygosity of 0.5, and occured with similar frequencies in teratozoospermic men (heterozygous n=11; homozygous minor n=4) and controls (heterozygous n=13; homozygous minor n=3). We identified a novel synonymous SNP in exon 1 (G54A) in two patients and one control. The G197T mutation in PRM1 previously reported¹ was not found. A meta-analysis of our and the literature data showed that the mutation G197T is not associated with teratozoospermia. Four SNPs were found in intron 1 of the PRM2 gene. C298G and C373A are listed in the NCBI database (rs1646022; rs2070923). The remaining two (C366T; C406T) were rare heterozygous SNPs, evenly distributed with a frequency of 3,4% in both groups. The prevalence of all SNPs was similar in infertile men and controls. No SNP was found in the exons.

Conclusion: Mutations of PRM1 and PRM2 are rare in teratozoospermic men with normal sperm count. Common polymorphisms of the PRM genes are not associated with idiopathic teratozoospermia.

(1) Iguchi, Yang, Lamb, Hecht (2006) J. Med. Genet. 43, 382–384.