Hum. Reprod. Advance Access originally published online on April 22, 2004
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Human Reproduction, Vol. 19, No. 6, 1338-1344,
June 2004
© 2004 European Society of Human Reproduction and Embryology
Developmental expression of POU5F1 (OCT-3/4) in normal and dysgenetic human gonads*
1 Department of Growth & Reproduction and 2 Department of Pathology, Copenhagen University Hospital (Rigshospitalet), DK-2100 Copenhagen, Denmark and 3 Section of Molecular Genetics and Infertility, Department of Gynaecological Endocrinology & Reproductive Medicine, University of Heidelberg, D-69120 Heidelberg, Germany
4 To whom correspondence should be addressed at: Department of Growth & Reproduction, Section 5064, Copenhagen University Hospital (Rigshospitalet), Blegdamsvej 9, DK-2100 Copenhagen, Denmark. e-mail: erm{at}rh.dk
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 
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.
Key words: germ cell differentiation/OCT-3/OCT-4/POU5F1/testicular carcinoma in situ
* Preliminary data were presented at the 42nd Annual ESPE Meeting, Ljubljana, Slovenia, September 2003.
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