Number №1, 2020 - page 96-104

Genetic forms of male infertility: main characteristics and practical aspects of laboratory diagnostics DOI: 10.29188/2222-8543-2020-12-1-96-104

For citation: Mikhaylenko D.S., Sobol I.Yu., Efremov E.A., Apolikhin O.I., Tanas A.S., Alekseev B.Ya., Nemtsova M.V. Genetic forms of male infertility: main characteristics and practical aspects of laboratory diagnostics. Experimental and clinical urology 2020;(1):96-104
Mihaylenko D.S., Sobol' I.Yu., Efremov E.A., Apolihin O.I., Tanas A.S., Alekseev B.Ya., Nemcova N.M.
Information about authors:
  • Mikhaylenko D.S. – PhD, Leading Researcher of scientific laboratory department of N.A. Lopatkin Scientific Research Institute of Urology and Interventional Radiology – Branch of the National Medical Research Centre of Radiology of the Ministry of Health of Russian Federation,  ORCID 0000-0001-9780-8708
  • Sobol I.Yu. – postgraduate student, Department of Andrology of Research Institute of Urology an Interventional Radiology – Branch of the National Medical Research Centre of Radiology of the Ministry of Health of Russian Federation
  • Efremov E.A. – Dr. Sc., Head of the Department of Andrology and Human Reproduction of N. Lopatkin Research Institute of urology and Interventional Radiology – branch of the National Medical Research Centre of Radiology of Ministry of health of Russian Federation, ORCID 0000-0001-7193-7413
  • Apolikhin O.I. – Dr. Sc, professor, сor.-member of RAS, director of N. Lopatkin Research Institute of urology and Interventional Radiology – branch of the National Medical Research Centre of Radiology of Ministry of health of Russian Federation, ORCID 0000-0003-0206-043X
  • Tanas A.S. – PhD, Leading researcher, Laboratory of Epigenetics, Research Centre for Medical Genetics named after Academician N.P. Bochkov, ORCID 0000-0002-2177-6743
  • Alekseev B.Ya. – Dr. Sc., professor, Deputy General Director for Science of the National Medical Research Centre of Radiology of Ministry of health of Russian Federation, ORCID 0000-0002-3398-4128
  • Nemtsova M.V. – prof., Head of Medical Genetics Laboratory, Institute of Molecular Medicine of the Scientific Technological Park of Biomedicine, Sechenov University, ORCID 0000-0002-2835-5992
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Background. Male infertility is an acute issue in modern andrology, being registered in 45% of infertile couples. Aer the exclusion of exogenous factors and systemic diseases leading to male infertility (MI), a significant part of MIcases among the remaining patients in the cohort with idiopathic infertility is associated with genetic pathologies.

Aim. To generalize data on genetic disorders that lead to a decrease in male fertility and to review methods of their diagnostics.

Material and methods. The main geneticforms of MI were reviewed:chromosome diseases (Klinefelter syndrome, de la Chapelle syndrome, etc.) and molecular-genetic disorders (AZF deletions, CFTR compound heterozygotes, the effect of low-penetrative polymorphisms). Special attention was paid to the application of highly-efficient next-generation sequencing (NGS)foridentification of germinal mutationsin coupleswith MIthrough sequencing of exome and target panels with a different number of genes.

Results.Genetic pathology isresponsible for a significantshare of MIcases and isrepresented by different genetic disorders, including chromosome aberrations (aneuploidy and deletions of different extension, point mutations in the coding parts of genes) and low-penetrative genetic variants. In the majority of MI caseswith a possible genetic background, karyotyping and analysis ofAZF deletions are performed forthe exclusion ofchromosome aberrations.In patients with obstructive MI, the analysis of frequent CFTR mutations is performed. Presently, genotyping of polymorphisms (CAG-repeat AR, gene family GST) has a low diagnostic value. Conversely, NGS technologies are becoming more widespread. An optimal method for direct DNA-diagnostics of mono- and oligogenic MI forms within one test consists in sequencing the coding parts of the respective gene-candidates as part of a specially selected target panel.

Conclusions. Prescription of genetic tests on the basis of minimal diagnostic criteria of known MI forms can significantly increase the reliability of laboratory diagnostics of male infertility.

Conflict of interest. The authors declare no conflict of interest.

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male infertility, diagnostics, genetics, mutation, polymorphism, DNA-diagnostics, PCR, sequencing, genotyping, chro- mosome aberrations, point mutations

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