Figure 6. Schematic illustration of the hypothesised origin of CIS from gonocytes.

Schematic illustration of the normal male germ cell development and possible transformation to CIS. ESCs are derived from the inner cell mass of a blastocyst. Prolonged culturing often leads to an accumulation of chromosomal aberrations, especially gain of material from chromosomes 12p and 17q. During early development, primordial germ cells migrate to the gonadal ridge and develop along the female (oogonia, top) or the male (gonocytes, bottom) germ cell lineage. In the male, the gonocytes become embedded in Sertoli cells, creating testicular cords. During the period from third trimester to 3 months postnatally, the gonocytes migrate to the periphery of the tubules and differentiate to pre-spermatogonia. After puberty, the spermatogonia proliferate and start spermatogenesis. CIS cells are proposed to arise when gonocytes fail to differentiate to pre-spermatogonia (1) and fail to undergo apoptosis (2). These gonocytes or pre-CIS cells lie dormant in the testis through infancy, while genomic aberrations may occur (3), and at puberty when testosterone levels increase, they start to proliferate and genomic aberrations accumulate, especially of chromosome 12 p and 17, eventually resulting in the formation of an overt tumor. Abbreviations: ICM, inner cell mass; ESC, embryonic stem cells; PGC, primordial germ cells; Sp-gonium, spermatogonium; EC, embryonal carcinoma; TER, teratoma; YST, yolk sac tumor; CHC, chorioncarcinoma.