[Pathogenesis of neoplastic changes in germ cells as a developmental aspect]

Fetal germ cells transform neoplastically probably at the fetal period of life. The best place for their maintenance is a testis with the disturbed organogenesis (differentiation). These testes are called dysgenetic gonads. Besides the classical form of gonadal dysgenesis, appearing by the reversed sex features (female in genetic males), there are probably hidden forms without the disturbances in the sex differentiation. The overt and hidden disturbances of the testes' organogenesis are called testicular dysgenesis syndrome (TDS). Gonadal dysgenesis is more frequent in normal male karyotype than in numerical and structural aberrations of sex chromosomes. The cause of TDS is an inappropriate expression of genes of Y chromosome or autosomes, taking part in testicular differentiation, and/or exposition to the influence of environmental factors, mainly with estrogen-like action. It is supposed that TDS determines a cascade of events leading to germ cell tumours (GCT). This mechanism may appear as follows: 1) the inhibited organogenesis of seminal tubules (sometimes at the level of sex cords) causes 2) the delay in differentiation and development of germ and somatic Sertoli/granulosa cells; 3) disturbed somatic cells contribute to the death of most germ cells, but germ cells which retain fetal antigens have the possibility to survive and proliferate; 4) if the survived germ cells are in the undifferentiated tissue of fetal gonad (retardation of testicular development at the level of gonadal anlage) their clonal expansion leads to the creation of neoplastic lesion termed gonadoblastoma. With time gonadoblastoma undergoes atrophy and/or calcification or may transform into GCT; 5) if the survived germ cells are placed inside the seminal tubules, they have better conditions to persist in the unchanged, but developmentally delayed, form for many years as preinvasive carcinoma in situ (CIS). CIS cells can disappear but with the advancing puberty they may give rise to GCT under the influence of gonadotropins and androgens.