Maturation delay of germ cells in fetuses with trisomy 21 results in increased risk for the development of testicular germ cell tumors.
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.
Cools
Martine
M
Department of Pathology, Josephine Nefkens Institute, Erasmus MC-University Medical Center, Daniel den Hoed, 3000 DR Rotterdam, The Netherlands.
Honecker
Friedemann
F
Stoop
Hans
H
Veltman
Joris D
JD
de Krijger
Ronald R
RR
Steyerberg
Ewout
E
Wolffenbuttel
Katja P
KP
Bokemeyer
Carsten
C
Lau
Yun-Fai Chris
YF
Drop
Stenvert L S
SL
Looijenga
Leendert H J
LH
D015415:Biomarkers / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism; D004314:Down Syndrome / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D005260:Female; D047109:Fetal Development; D005854:Germ Cells / Q000254:growth & development* / Q000378:metabolism / Q000473:pathology; D006066:Gonads / Q000002:abnormalities / Q000254:growth & development* / Q000378:metabolism; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009373:Neoplasms, Germ Cell and Embryonal / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D050814:Octamer Transcription Factor-3 / Q000378:metabolism; D013736:Testicular Neoplasms / Q000150:complications* / Q000378:metabolism / Q000473:pathology
D015415:Biomarkers; D018797:Cell Cycle Proteins; D050814:Octamer Transcription Factor-3; C497749:TSPY1 protein, human