Trisomy 21 is associated with an increased risk for the occurrence of germ cell tumors in males. The development of these tumors is thought to be related to events in fetal life. A delay in the maturation of germ cells is one of the mechanisms that have been proposed for the development of these tumors in high-risk groups such as intersex patients. To investigate whether a delay in germ cell development also occurs in trisomy 21, we examined the gonads of 30 fetuses, neonates, and infants with trisomy 21 (19 males and 11 females) for the expression of several immunohistochemical germ cell markers throughout pregnancy and compared them with a series of 46 age-matched controls. The results of our study reveal a significant delay in germ cell development in fetuses with trisomy 21, especially in males. Prolonged expression of octamer binding transcription factor 3/4, in combination with an increased expression of testis-specific protein, Y-encoded, might have pathogenetic relevance for the development of testicular germ cell tumors in this population.

Germ cell neoplasia, Gonadal development, OCT3/4, Trisomy 21, TSPY,
Human Pathology
Department of Pathology

Cools, M.B.C.M, Honecker, F.U, Stoop, J.A, Veltman, J.D, de Krijger, R.R, Steyerberg, E.W, … Looijenga, L.H.J. (2006). Maturation delay of germ cells in fetuses with trisomy 21 results in increased risk for the development of testicular germ cell tumors. Human Pathology, 37(1), 101–111. doi:10.1016/j.humpath.2005.09.021