Relevance of the β-defensin family in reduction of male reproductive function

• Elena M. Khasanova
• Lyudmila V. Gankovskaya
• Vyacheslav V. Grechenko
• Oksana A. Svitich

Abstract

Introduction. Nowadays infertility became a global sociodemographic problem, which affects about 15 % of couples around the world. In the last few years more and more studies, which research an influence of antimicrobial peptides of the β-defensins family on reproductive processes, have been appearing.

The aim of this study was to estimate the role of β-defensins HBD1 and HBD26 in the pathogenesis of male infertility and the association of carriership of mutant HBD126 gene del allele (rs11468374) with its’ gene expression levels in sperm cells, and the level of its’ protein product in the seminal fluid of infertile patients.

Material and methods. The study included 88 male subjects. The participants were divided into a group of 65 men affected by idiopathic infertility, and a group of 23 healthy donors. Separation of the ejaculate into seminal fluid and spermatozoa was performed via centrifugation of the ejaculate in a density gradient. To assess the DEFB1, DEFB126 genes expression and the polymorphic marker (rs11468374) of DEFB126 gene, the techniques of DNA/RNA extraction, reverse transcription reaction, and real time PCR were used. The level of the HBD1, HBD26 peptides in the semen fluid was assessed by enzyme-linked immunosorbent assay.

Results. We demonstrated a decrease of expression of DEFB1 and DEFB126 genes in spermatozoa of patients with idiopathic infertility with severe asthenozoospermia by 4.5 times (HBD1) and 13.57 (HBD26) in comparison with heathy donors, with the concentration levels of these defensins in seminal plasma reduced by 2.7 and 13.84 times respectively. We also estimated a distribution of allele and genotype frequencies of the rs11468374 polymorphic marker of the DEFB126 gene among Moscow population. We demonstrated that the carriership of the mutant del allele is statistically associated with a higher risk of impairment of male fertility (χ² = 14.67, р < 0.001, OR = 6.83; 95 % CI 2.409-19.366).

Conclusion. These data can be used for a more detailed study of β-defensins’ influence on male reproduction processes and establishment of infertility. Also the results of our work could be a foundation of an early diagnosis of susceptibility to decrease of fertility function.

Keywords:innate immunity; male infertility; β-defensin; sperm cells; sperm motility

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