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Option of a chemical compound with a combined spermatotoxic effect to create a model of controlled toxic damage of spermatogenesis

DOI 10.18127/j20700997-201903-01


A.A. Kamalov −
Dr. Sc. (Med.), Professor, Academician RAS, Director, Medical Research and Education Center
of Lomonosov Moscow State University; Head of Department of Urology and Andrology,
Faculty of Fundamental Medicine, Lomonosov Moscow State University
D.A. Ohobotov −
Ph.D. (Med.), Urologist, Medical Research and Education Center of Lomonosov Moscow State University;
Associate Professor, Department of Andrology and Urology, Faculty of Fundamental Medicine,
Lomonosov Moscow State University
A.Yu. Efimenko −
Ph. D. (Med.), Senior Research Scientist, Institute for Regenerative Medicine,
Medical Research and Education Center of Lomonosov Moscow State University
G.D. Sagaradze −
Laboratory Assistant, Institute for Regenerative Medicine, Lomonosov Moscow State University
M.E. Chaliy –
Dr.Sc. (Med.), Professor, Leading Research Scientist, Medical Research and Education Center
of Lomonosov Moscow State University;
A.N. Nizov –
Urologist, Junior Research Scientist, Moscow Research and Education Center
of Lomonosov Moscow State University,
V.K. Dzitiev –
Ph.D. (Med.), Head of Urological Service, Medical Research and Education Center
of Lomonosov Moscow State University
E.V. Afanasyevskaya –
Resident Physician, Department of Urology and Andrology, Faculty of Fundamental Medicine,
Lomonosov Moscow State University
A.A. Strigunov –
Resident Physician, Department of Urology and Andrology, Faculty of Fundamental Medicine,
Lomonosov Moscow State University
O.Y. Nesterova –
Student, Faculty of Fundamental Medicine, Lomonosov Moscow State University

Spermatogenesis is a process of division and differentiation of sperm, which includes three stages: spermatocytogenesis, meiosis and spermatogenesis. At the first stage there is a mitotic division of stem cells with the formation of primary spermatocytes. Meiosis leads to the formation of four haploid spermatids. Spermatogenesis consists in the differentiation of spherical sperm into mature cells in the absence of their division.
The most severe damage during spermatogenesis is observed at the stage of spermatocytogenesis. In addition to the effects of endogenous hormones, the spermatogenic epithelium is daily exposed to a number of exogenous factors. Male sex cells are extremely sensitive to elevated temperatures, malnutrition, androgenic drugs, toxic effects of metals, x-rays, dioxins, alcohol, infectious agents and other factors. These factors can cause a temporary or permanent response, characterized by a decrease in the total number of germ cells, both in absolute values and relative to Sertoli cells, as well as the formation of multinuclear giant layers.
With the development of pharmacotherapy, it became clear that many drugs, in addition to their main therapeutic action, can affect other organs, including the testes, providing spermatotoxic effect on the main stages of spermatogenesis. In addition to drugs, other substances contained in exhaust gases, tobacco smoke, water and even food have a negative impact on the development and differentiation of sperm. Due to the presence of such a variety of exogenous effects, we have analyzed the available literature data with a review of experimental models for the study of spermatotoxic action of drugs in order to develop a biological model of controlled toxic damage of spermatogenesis.
It was found that the most persistent and irreversible disorders occur against the background of taking anticancer drugs, bu-sulfan, cytostatics, heavy metal salts, mycotoxins and polycyclic aromatic hydrocarbons. The other classes of pharmacothera-peutic agents cause temporary disorders that can be compensated after discontinuation of these drugs.
To assess the proposed protective mechanisms of action of new drugs for the recovery of spermatogenesis in toxic damage, it is most appropriate to use busulfan, cytostatic and heavy metal salt damage models, as the mechanisms of the damaging effects of these drugs are well described in the literature, the models are repeatable and allow to obtain a clear histomorphological picture.

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May 29, 2020

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