Molecular mechanisms of male infertility: main directions of scientific research


Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access

Abstract

This review provides up-to-date information on the molecular basis of the pathogenesis of male infertility at the cellular and subcellular levels. The emphasis is on the importance of new next-generation sequencing technologies as a high-performance tool for studying the genome and epigenomic mechanisms, transcriptome, proteome and metabolome of ejaculate, and organs of the reproductive system. This methodology made it possible to identify differentially expressed metabolic and signaling pathways in fertile and infertile men that combine the genotype and phenotype of a particular individual into a single whole. The current ideas about the relationship between oxidative stress and imbalance of redox systems with DNA damage in spermatozoa as the leading mechanism for the development of idiopathic infertility are summarized. The role of miRNAs, methyloma aberrations, deficiency of phospholipase C zeta in spermatozoa in the pathology of fertility is given. Deciphering the molecular profile and molecular phenotypes of infertility as a result of the interaction of genetic and environmental factors is a necessary condition for screening the most informative biomarkers, assessing their stratification potential, and validating new molecules as potential targets for targeted therapy.

Full Text

Restricted Access

About the authors

S. N Galimov

Bashkir StateMedical University

Email: sngalim@mail.ru
MD, PhD, DSc, Professor, Head of the Department of Biological Chemistry

Yu. Yu Gromenko

Medical Center Family

Email: info@medufa.ru
MD, PhD, Head Physician

K. Sh Galimov

I.M.Sechenov First Moscow State Medical University (Sechenov University)

Email: sngalim@mail.ru
Student, N.V. Sklifosovsky Institute of Clinical Medicine

E. F Galimova

Bashkir StateMedical University

Email: efgalimova@mail.ru
MD, Professor of the Department of Pathological Physiology

E. S Bodrova

I.M.Sechenov First Moscow State Medical University (Sechenov University)

Email: elizaveta5976@mail.ru
student of the Institute of Clinical Medicine named after N.V. Sklifosovsky

K. V Bulygin

I.M.Sechenov First Moscow State Medical University (Sechenov University); M.V.Lomonosov Moscow State University

Email: kirill-bh-red@yandex.ru
MD, PhD, Associate Professor of the Department of Human Anatomy; Associate Professor at the Department of Normal and Topographic Anatomy

P. F Litvitsky

I.M.Sechenov First Moscow State Medical University (Sechenov University)

Email: litvitskiy_p_f@staff.sechenov.ru
MD, PhD, DSc, Professor, Head of the Department of Pathophysiology

References

  1. Baskaran S., Agarwal A., Leisegang K., Pushparaj P., Panner Selvam M., Henkel R. An In-Depth Bibliometric Analysis and Current Perspective on Male infertility Research.World. J. Mens. Health. 2021;39(2):302-314. doi: 10.5534/wjmh.180114.
  2. Agarwal A., Mulgund A., Hamada A., Chyatte M. A unique view on male infertility around the globe. ReprodBiolEndocrinol. 2015;13:37. doi: 10.1186/s12958-015-0032-1.
  3. Pavlov V.N., Galimova E.F., Akhmadullina G.H., Galimov Sh.N. Medico-biological, social, cultural and educational aspects of men’s health protection. Preventive and clinical medicine. 2014;2(51):5-13. Russan (Павлов В.Н., Галимова Э.Ф., Ахмадуллина Г.Х., Галимов Ш.Н. Медико-биологические, социальные и культурно-образовательные аспекты охраны мужского здоровья. Профилактическая и клиническая медицина. 2014;2(51):5-13).
  4. Lebedev G.S., Golubev N.A., Shaderkin I.A., Shaderkina V.A., Apolikhin O.I., Sivkov A.V. Male infertility in the Russian Federation: statistical data for 2000 2018 Experimental and clinical urology. 2019;4:4-12. Russoan (Лебедев Г.С., Голубев Н.А., Шадеркин И.А., Шадеркина В.А., Аполихин О.И., Сивков А.В. Мужское бесплодие в Российской Федерации: статистические данные за 2000-2018 гг. Экспериментальная и клиническая урология. 2019;4:4-12). doi: 10.29188/2222-8543-2019 11-4-4-12.
  5. Houston B., Riera-Escamilla A., Wyrwoll M., Salas-Huetos A., Xavier M., Nagirnaja L. et al. A systematic review of the validated monogenic causes of human male infertility: 2020 update and a discussion of emerging gene-disease relationships. Hum. Reprod. Update. 2021:dmab030. doi: 10.1093/humupd/dmab030.
  6. Aitken R. The Male Is Significantly Implicated as the Cause of Unexplained Infertility. Semin. Reprod. Med. 2020;38(1):3-20. doi: 10.1055/s-0040-1718941.
  7. Shiraishi K. Genome medicine in male infertility: From karyotyping to single-cell analysis. J. Obstet. Gynaecol. Res. 2021;47(8):2586-2596. doi: 10.1111/jog.14828.
  8. Pavlov V.N., Galimova E.F., Teregulov B.F., Kaibyshev V.T., Galimov S.N. Molecular and metabolic aspects of male infertility. Bulletin of Urology. 2016;2:40-49. Rusian (Павлов В.Н., Галимова Э.Ф., Терегулов Б.Ф., Кайбышев В.Т., Галимов Ш.Н. Молекулярные и метаболические аспекты мужского бесплодия. Вестник урологии. 2016;2:40-49).
  9. Craig J., Jenkins T., Carrell D., Hotaling J. Obesity, male infertility, and the sperm epigenome. Fertil. Steril. 2017;107:848-859. Doi: 10.1016/j. fertnstert.2017.02.115.
  10. Ilacqua A., Izzo G., PietroEmerenziani G., Baldari C., Aversa A. Lifestyle and fertility: the influence of stress and quality of life on male fertility. Reprod. Biol. Endocrinol. 2018;16:115. doi: 10.1186/s12958-018-0436-9.
  11. Agarwal A., Baskaran S., Parekh N. et al. Male infertility. Lancet. 2021;397(10271):319-333. doi: 10.1016/S0140-6736(20)32667-2.
  12. Salas-Huetos A., Aston K.I. Defining new genetic etiologies of male infertility: progress and future prospects. Transl. Androl. Urol. 2021;10(3):1486-1498. doi: 10.21037/tau.2020.03.43.
  13. Krausz C., Riera-Escamilla A. Genetics of male infertility. Nat. Rev. Urol. 2018;15:369-384. doi: 10.1038/s41585-018-0003-3.
  14. Aitken R., Drevet J. The Importance of Oxidative Stress in Determining the Functionality of Mammalian Spermatozoa: A Two-Edged Sword. Antioxidants. 2020;9:111. doi: 10.3390/antiox9020111.
  15. Lord T., Aitken R. Fertilization stimulates 8-hydroxy-2’-deoxyguanosine repair and antioxidant activity to prevent mutagenesis in the embryo. Dev. Biol. 2015;406:1-13. doi: 10.1016/j.ydbio.2015.07.024.
  16. Xavier M., Nixon B., Roman S., Scott R., Drevet J., Aitken R. Paternal impacts on development: identification of genomic regions vulnerable to oxidative DNA damage in human spermatozoa. Hum Reprod. 2019;34:1876-1890. doi: 10.1093/humrep/dez153.
  17. Aitken R., Baker M. The Role of Genetics and Oxidative Stress in the Etiology of Male Infertility - A Unifying Hypothesis? Front. Endocrinol. 2020;11:581838. doi: 10.3389/fendo.2020.581838/.
  18. Galimov Sh., Gromenko J., Bulygin K., Galimov K., Galimova E., Sinelnikov M. The level of secondary messengers and the redox state of NAD+/NADH are associated with sperm quality in infertility. J. Reprod. Immunol. 2021;148:103383. doi: 10.1016/j.jri.2021.103383.
  19. Baskaran S., Finelli R., Agarwal A., Henkel R. Reactive oxygen species in male reproduction: A boon or a bane? Andrologia. 2021;53(1):e13577. doi: 10.1111/and.13577.
  20. Гяургиев Т.А., Кузьменко А.В., Кузьменко В.В. Современный взгляд на применение антиоксидантов в терапии мужского бесплодия. 2020;6:142-147. doi: 10.18565/urology.2020.6.142-147.
  21. Cannarella R., Condorelli R., Mongioi L., La Vignera S., Calogero A. Molecular Biology of Spermatogenesis: Novel Targets of Apparently Idiopathic Male Infertility. Int. J. Mol. Sci. 2020;21(5):1728. doi: 10.3390/ijms21051728.
  22. Lombo M., Ruiz-Diaz S., Gutierrez-Adan A., SanchezCalabuig M. Sperm Metabolomics through Nuclear Magnetic Resonance Spectroscopy. Animals (Basel). 2021;11(6):1669. doi: 10.3390/ani11061669.
  23. McSwiggin H., O’Doherty A. Epigenetic reprogramming during spermatogenesis and male factor infertility. Reproduction. 2018;156:9-21. doi: 10.1530/REP-18-0009.
  24. Rotondo J., Lanzillotti C., Mazziotta C. et al. Epigenetics of Male Infertility: The Role of DNA Methylation. Front. Cell Dev. Biol. 2021;9:689624. doi: 10.3389/fcell.2021.689624.
  25. Sarkar S., Sujit K., Singh V., Pandey R., Trivedi S., Singh K. Array-based DNA methylation profiling reveals peripheral blood differential methylation in male infertility. FertilSteril. 2019;112(1):61-72.e1. Doi: 10.1016/j. fertnstert.2019.03.020.
  26. Barbu M., Thompson D., Suciu N., Voinea S., Cretoiu D., Predescu D. The Roles of MicroRNAs in Male Infertility. Int. J. Mol. Sci. 2021;22(6):2910. doi: 10.3390/ijms22062910.
  27. Eikmans M., Anholts J., Blijleven L., Meuleman T., van Beelen E., van der Hoorn M. Optimization of microRNA Acquirement from Seminal Plasma and Identification of Diminished Seminal microRNA-34b as Indicator of Low Semen Concentration. Int. J. Mol. Sci. 2020;21(11):4089. doi: 10.3390/ijms21114089.
  28. Wang C., Yang C., Chen X., Yao B., Yang C., Zhu C. et al. Altered profile of seminal plasma microRNAs in the molecular diagnosis of male infertility. Clin. Chem. 2011;57(12):1722-1731. doi: 10.1373/clinchem.2011.169714.
  29. Mostafa T., Rashed L., Nabil N., Osman I. Mostafa R. Farag M. Seminal miRNA Relationship with Apoptotic Markers and Oxidative Stress in Infertile Men with Varicocele. Biomed. Res. Int. 2016;2016:4302754. doi: 10.1155/2016/4302754.
  30. Tian H., Lv M., Li Z., Peng D., Tan Y., Wang H. et al. Semen-specific miRNAs: Suitable for the distinction of infertile semen in the body fluid identification? Forensic Sci. Int. Genet. 2018;33:161-167. Doi: 10.1016/j. fsigen.2017.12.010.
  31. Corral-Vazquez C., Salas-Huetos A., Blanco J., Vidal F., Sarrate Z., Anton E. Sperm microRNA pairs: new perspectives in the search for male fertility biomarkers. FertilSteril. 2019;112(5):831-841. Doi: 10.1016/j. fertnstert.2019.07.006.
  32. Галимова Э.Ф., Павлов В.Н., Абдуллина А.З., Галимов Ш.Н. Особенности ферментного профиля и энергетического статуса спермальной плазмы при идиопатическом бесплодии. Проблемы репродукции. 2013;1:66-69
  33. Park Y., Pang M. Mitochondrial Functionality in Male Fertility: From Spermatogenesis to Fertilization. Antioxidants (Basel). 2021;10(1):98. doi: 10.3390/antiox10010098.
  34. Громенко Ю.Ю., Галимова Э.Ф., Громенко Д.Д., Галимов К.Ш., Булыгин К.В., Галимов Ш.Н. Активация ооцитов: фундаментальные и клинические аспекты. Вопросы гинекологии, акушерства и перинатологии. 2020;19(5):77-85. doi: 10.20953/17261678-2020-5-77-85.
  35. Cardona Barberan A., Boel A., VandenMeerschaut F., Stoop D., Heindryckx B. Diagnosis and Treatment of Male Infertility-Related Fertilization Failure. J.Clin. Med. 2020;9(12):3899. doi: 10.3390/jcm9123899.
  36. Meng X., Melo P., Jones C., Ross C., Mounce G., Turner K. et al. Use of phospholipase C. zeta analysis to identify candidates for artificial oocyte activation: a case series of clinical pregnancies and a proposed algorithm for patient management. FertilSteril. 2020;114(1):163-174. Doi: 10.1016/j. fertnstert.2020.02.113.
  37. Kumar N., Singh N. Emerging role of Novel Seminal Plasma Biomarkers in Male Infertility: A Review. Eur. J. Obstet. Gynecol. Reprod. Biol. 2020;253:170-179. doi: 10.1016/j.ejogrb.2020.08.015.
  38. Галимов Ш.Н., Божедомов В.А., Галимова Э.Ф., Павлов В.Н., Сухих Г.Т. Мужское бесплодие: молекулярные иммунологические аспекты. М.: ГЭОТАР-Медиа. 2020; 208 с.

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2022 Bionika Media

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies