Abstract
Protamine (PRM) plays important roles in the packaging of DNA within the sperm nucleus. To investigate the role of PRM1/2 and transition protein 1 (TNP1) polymorphisms in male infertility, 636 infertile men and 442 healthy individuals were recruited into this case-controlled study of the Chinese Han population, using MassARRAY technology to analyze genotypes. Our analysis showed that there were no significant differences between controls and infertile cases among the five single nucleotide polymorphisms identified in PRM1, PRM2 and TNP1 [rs737008 (G/A), rs2301365 (C/A), rs2070923 (C/A), rs1646022 (C/G) and rs62180545 (A/G)]. However, we found that the PRM1 and PRM2 haplotypes GCTGC, TCGCA and TCGCC exhibited significant protective effects against male infertility compared to fertile men, while TCGGA, GCTCC and TCGGC represented significant risk factors for spermatogenesis. Our data showed that rs737008 and rs2301365 in PRM1, and rs1646022 in PRM2, were significantly associated with male infertility and that gene–gene interaction played a role in male infertility. A linkage disequilibrium plot for the five SNPs showed that rs737008 was strongly linked with both rs2301365 and rs2070923. These findings are likely to help improve our understanding of the etiology of male infertility. Further studies should include a larger number of genes and SNPs, particularly growing critical genes; such studies will help us to unravel the effect of individual genetic factors upon male infertility.
Highlights
Approximately 15% of heterosexual couples suffer from infertility [1,2,3,4,5,6], in which non-obstructive azoospermia (NOA) and severe oligozoospermia represent two of the predominant phenotypes relating to severely defective spermatogenesis
Our analysis showed that there were no significant differences between controls and infertile cases among the five single nucleotide polymorphisms identified in protamine 1 (PRM1), protamine 2 (PRM2) and transition protein 1 (TNP1) [rs737008 (G/A), rs2301365 (C/A), rs2070923 (C/A), rs1646022 (C/G) and rs62180545 (A/G)]
Two types of protamine were identified in mammals: protamine 1 (PRM1), which is present in vertebrate species, and protamine 2 (PRM2), which only exists in some mammalian species, including humans and mice [8]
Summary
Approximately 15% of heterosexual couples suffer from infertility [1,2,3,4,5,6], in which non-obstructive azoospermia (NOA) and severe oligozoospermia represent two of the predominant phenotypes relating to severely defective spermatogenesis. Several factors can lead to male infertility, including malformations of the reproductive tract (e.g., varicocele or cryptorchidism, hypogonadotrophic hypogonadism, karyotype anomalies and Y chromosome microdeletions), infection, and chemical exposure, the effect of genetic predisposition upon male infertility remains to be fully clarified [2]. PRM1 and PRM2 (NC_000016.9, GI: 224589807) are closely linked in a stretch of DNA 13– 15 kb long on human chromosome 16p13.3, along with the gene encoding transition protein 2 (TNP2); collectively, these genes are categorized as members of the protamine gene family [2]. Mutations or polymorphisms within PRM induce conformational changes of the encoded proteins and alter their incorporation into sperm chromatin, leading to sperm defects, the underlying mechanisms remain largely unknown [8, 9]. Considered as one of the most perplexing disorders in the reproductive field, male factor infertility is prevalent, and its incidence is rising; worryingly, the etiology of this condition remains largely elusive
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