Моlecular mechanisms of initiation of carcinogenesis in the testis

In this review, literature data on the study of precancerous changes in testicular tissue and molecular changes, as well as the influence of environmental factors that can initiate carcinogenesis, were analyzed and summarized for the future determination of early diagnosis of germ cell tumors of the testis and the development of preventive measures. The review also discusses the significant new changes presented in the Fourth Edition of the World Health Organization Classification of Urogenital Tumors, published in 2016, and modern concepts of the etiology and pathogenesis of these diseases. Among the environmental factors that can initiate carcinogenesis, the most noteworthy are the biological effects of low doses of ionizing radiation, such as the effect of radiation-induced genome instability, which increases the risk of carcinogenesis, the "bystander effect", and chronic oxidative stress. Disruption of ubiquitin-proteasomal proteolysis, impaired molecular-level components of the blood-testis barrier, and impaired regulatory action of TGF-β on the cell cycle can play a crucial role in the pathogenesis of male infertility and the initiation of carcinogenesis in the testis. The effect of low doses of ionizing radiation as an additional etiological factor leads to changes in the structural, as well as molecular, components of the testis, including epigenetic changes, which can be characterized as environmental pathomorphosis, which leads to impaired spermatogenesis and increased risk of malignancy. Summarizing the literature review data, we can state that patients with blocked spermatogenesis, in which atypical germ cell neoplasia in situ cells are detected in testicular tissue, constitute a group at increased risk of testicular carcinogenesis. The presence of additional etiological factors, such as chronic low doses of ionizing radiation, can initiate the progression of carcinogenesis in the testicle.