Developmental expression of POU5F1 (OCT-3/4) in normal and dysgenetic human gonads.
BACKGROUND
To investigate how long fetal germ cells retain pluripotency, which may be linked to their ability to transform into histologically variable tumours, we examined the expression of OCT-3/4 (POU5F1), a transcription factor essential for the maintenance of totipotency in embryonic stem cells.


METHODS
The ontogeny of expression of OCT-3/4 was studied in 74 specimens of normal human gonads during development and in 58 samples of gonads from cases with testicular dysgenesis syndrome (TDS), including disorders of sex differentiation and malignant changes.


RESULTS
OCT-3/4 expression was found in primordial germ cells during migration to the gonadal ridges and in the indifferent gonad. The expression in testes gradually decreased until approximately 20 weeks of gestation, and thereafter it was more rapidly down-regulated, but persisted in a few cells until 3-4 months of postnatal age, which coincides with the final differentiation of gonocytes into infantile spermatogonia. Subsequently, OCT-3/4 was not detected in normal testes. In the ovaries, OCT-3/4 was expressed in primordial oogonia, but was down-regulated in oocytes that formed primary follicles. The pattern of expression was heterogeneous in dysgenetic and intersex cases, with OCT-3/4-positive gonocytes detected in this series until 14 months of age. Visibly neoplastic gonadoblastoma and carcinoma in situ (CIS) expressed abundant OCT-3/4 regardless of the age.


CONCLUSIONS
In the human ovary, OCT-3/4 is silenced at the onset of the first meiotic prophase, whereas in the testis, down-regulation of OCT-3/4 is a gradual process associated with differentiation of gonocytes. This normal pattern of expression is disturbed in dysgenetic gonads, especially in rare intersex cases, thus increasing the risk of malignant transformation. The high abundance of OCT-3/4 in CIS cells is consistent with their early fetal origin and pluripotency.
Rajpert-De Meyts
Ewa
E
Department of Growth & Reproduction, Copenhagen University Hospital (Rigshospitalet), Copenhagen, Denmark. erm@rh.dk
Hanstein
Regina
R
Jørgensen
Niels
N
Graem
Niels
N
Vogt
Peter H
PH
Skakkebaek
Niels E
NE
D002102:Cadaver; D016022:Case-Control Studies; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004622:Embryo, Mammalian / Q000378:metabolism; D047108:Embryonic Development; D005260:Female; D020868:Gene Silencing; D018237:Germinoma / Q000196:embryology; D006059:Gonadal Dysgenesis / Q000196:embryology*; D006801:Humans; D008297:Male; D050814:Octamer Transcription Factor-3; D010053:Ovary / Q000196:embryology*; D013737:Testis / Q000196:embryology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D004268:DNA-Binding Proteins; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; D014157:Transcription Factors