title: Maturation delay of germ cells in fetuses with trisomy 21 results in increased risk for the development of testicular germ cell tumors.
abstract: 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.
authors.affiliation: Department of Pathology, Josephine Nefkens Institute, Erasmus MC-University Medical Center, Daniel den Hoed, 3000 DR Rotterdam, The Netherlands.
authors.forename: Martine
authors.initials: M
authors.lastname: Cools
authors.forename: Friedemann
authors.initials: F
authors.lastname: Honecker
authors.forename: Hans
authors.initials: H
authors.lastname: Stoop
authors.forename: Joris D
authors.initials: JD
authors.lastname: Veltman
authors.forename: Ronald R
authors.initials: RR
authors.lastname: de Krijger
authors.forename: Ewout
authors.initials: E
authors.lastname: Steyerberg
authors.forename: Katja P
authors.initials: KP
authors.lastname: Wolffenbuttel
authors.forename: Carsten
authors.initials: C
authors.lastname: Bokemeyer
authors.forename: Yun-Fai Chris
authors.initials: YF
authors.lastname: Lau
authors.forename: Stenvert L S
authors.initials: SL
authors.lastname: Drop
authors.forename: Leendert H J
authors.initials: LH
authors.lastname: Looijenga
mesh_terms: 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
chemical_list: D015415:Biomarkers; D018797:Cell Cycle Proteins; D050814:Octamer Transcription Factor-3; C497749:TSPY1 protein, human