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The Nsun7 (A11337)-deletion mutation, causes reduction of its protein rate and associated with sperm motility defect in infertile men

  • Genetics
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Abstract

Purpose

Recent studies have shown that genetic abnormalities may be responsible for most unknown cases of male infertility. Human Nsun7 gene, which is located on chromosome4, has a role in sperm motility by encoding the putative methyltransferase Nsun7 protein. The aim of the present study was to investigate the mutations of exon4 in the Nsun7 gene, which is associated with sperm motility defect.

Methods

Semen samples including those of fertile normospermic (normal), infertile oligospermic (with normal sperm motility), and infertile asthenospermic (with reduced sperm motility) men were collected from the Omid and Fatemezahra IVF centres (Babol, Iran). These samples were then analysed on the basis of World Health Organization guidelines using the general phenol–chloroform DNA extraction method. Exon4 was amplified using Sun-F/Sun-R primers. Samples from asthenospermic men, which showed different patterns of movement on single-strand conformation polymorphism compared with normal and oligospermic samples, were identified and subjected to sequencing for further identification of possible mutations.

Results

Analysis of extracted sperm proteins showed that the rate of Nsun7 decreased. Likewise, direct sequencing of PCR products, along with their analysis, confirmed the deletion mutation of adenine in location 11337 of the Nsun7 gene in asthenospermic men. Comparison of normal and mutant protein structures of Nsun7 indicated that the A11337-deletion of the exon4 resulted in the valine residues-157 with GTA-codon in normospermic replaced with TAG-early stop codon in asthenospermic samples, causing an abortive protein product with amino acid sequence shorter than normal. The secondary structure of the protein, the protein folding, and ligand binding sites were changed, indicating the impairment of the protein function.

Conclusions

Because the Nsun7 gene products have a role in sperm motility, it will lead to impairment in the activity of the protein and motility of sperm flagella as well as male infertility if a mutation occurs in this gene.

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Acknowledgments

Thanks to Dr. Seyed Golam Ali Jorsaraei, from Fatemeh Zahra Hospital (Babol Iran), for sample preparation and persons who helped prepare the manuscript and helped us to revise the paper.

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Authors and Affiliations

  1. Department of Molecular and Cell Biology, Faculty of Basic Sciences, University of Mazandaran, Babolsar, CP 47416-95447, Iran

    Nahid Khosronezhad, Abasalt Hosseinzadeh Colagar & Seyed Mohsen Mortazavi

Authors
  1. Nahid Khosronezhad
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  2. Abasalt Hosseinzadeh Colagar
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  3. Seyed Mohsen Mortazavi
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Corresponding author

Correspondence to Abasalt Hosseinzadeh Colagar.

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Capsule

Our results indicate that there is an association between the exon 4 mutation in Nsun7 gene and sperm motility defect with male infertility in an Iranian population, hence the A11337-Deletion mutation in exon 4 of the Nsun7 gene can be used as an indicator of infertility.

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Khosronezhad, N., Hosseinzadeh Colagar, A. & Mortazavi, S.M. The Nsun7 (A11337)-deletion mutation, causes reduction of its protein rate and associated with sperm motility defect in infertile men. J Assist Reprod Genet 32, 807–815 (2015). https://doi.org/10.1007/s10815-015-0443-0

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  • DOI: https://doi.org/10.1007/s10815-015-0443-0

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