Hum. Reprod. Advance Access originally published online on April 22, 2004
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  B. Wang, L. Li, F. Ni, J. Song, J. Wang, Y. Mu, X. Ma, and Y. Cao Mutational analysis of SAL-Like 4 (SALL4) in Han Chinese women with premature ovarian failure Mol. Hum. Reprod., September 1, 2009; 15(9): 557 - 562. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. B. Sonne, K. Almstrup, M. Dalgaard, A. S. Juncker, D. Edsgard, L. Ruban, N. J. Harrison, C. Schwager, A. Abdollahi, P. E. Huber, et al. Analysis of Gene Expression Profiles of Microdissected Cell Populations Indicates that Testicular Carcinoma In situ Is an Arrested Gonocyte Cancer Res., June 15, 2009; 69(12): 5241 - 5250. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Nonaka Differential Expression of SOX2 and SOX17 in Testicular Germ Cell Tumors Am J Clin Pathol, May 1, 2009; 131(5): 731 - 736. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. M. Sturgeon, M. J. Duffy, U.-H. Stenman, H. Lilja, N. Brunner, D. W. Chan, R. Babaian, R. C. Bast Jr., B. Dowell, F. J. Esteva, et al. National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines for Use of Tumor Markers in Testicular, Prostate, Colorectal, Breast, and Ovarian Cancers Clin. Chem., December 1, 2008; 54(12): e11 - e79. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R.T. Mitchell, G. Cowan, K.D. Morris, R.A. Anderson, H.M. Fraser, K.J. Mckenzie, W.H.B. Wallace, C.J.H. Kelnar, P.T.K. Saunders, and R.M. Sharpe Germ cell differentiation in the marmoset (Callithrix jacchus) during fetal and neonatal life closely parallels that in the human Hum. Reprod., December 1, 2008; 23(12): 2755 - 2765. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Sa, R. Neves, S. Fernandes, C. Alves, F. Carvalho, J. Silva, N. Cremades, I. Malheiro, A. Barros, and M. Sousa Cytological and Expression Studies and Quantitative Analysis of the Temporal and Stage-Specific Effects of Follicle-Stimulating Hormone and Testosterone During Cocultures of the Normal Human Seminiferous Epithelium Biol Reprod, November 1, 2008; 79(5): 962 - 975. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. F. Gjerstorff, L. Harkness, M. Kassem, U. Frandsen, O. Nielsen, M. Lutterodt, K. Mollgard, and H. J. Ditzel Distinct GAGE and MAGE-A expression during early human development indicate specific roles in lineage differentiation Hum. Reprod., October 1, 2008; 23(10): 2194 - 2201. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. J. Childs, P. T.K. Saunders, and R. A. Anderson Modelling germ cell development in vitro Mol. Hum. Reprod., September 1, 2008; 14(9): 501 - 511. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. M. Kristensen, J. E. Nielsen, N. E. Skakkebaek, N. Graem, G. K. Jacobsen, E. R.-D. Meyts, and H. Leffers Presumed pluripotency markers UTF-1 and REX-1 are expressed in human adult testes and germ cell neoplasms Hum. Reprod., April 1, 2008; 23(4): 775 - 782. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. L. Kerr, C. M. Hill, P. D. Blumenthal, and J. D. Gearhart Expression of pluripotent stem cell markers in the human fetal ovary Hum. Reprod., March 1, 2008; 23(3): 589 - 599. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. F. Gjerstorff, K. Kock, O. Nielsen, and H. J. Ditzel MAGE-A1, GAGE and NY-ESO-1 cancer/testis antigen expression during human gonadal development Hum. Reprod., April 1, 2007; 22(4): 953 - 960. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. M. Wikstrom, C. E. Hoei-Hansen, L. Dunkel, and E. Rajpert-De Meyts Immunoexpression of Androgen Receptor and Nine Markers of Maturation in the Testes of Adolescent Boys with Klinefelter Syndrome: Evidence for Degeneration of Germ Cells at the Onset of Meiosis J. Clin. Endocrinol. Metab., February 1, 2007; 92(2): 714 - 719. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C.E. Hoei-Hansen, E. Carlsen, N. Jorgensen, H. Leffers, N.E. Skakkebaek, and E. Rajpert-De Meyts Towards a non-invasive method for early detection of testicular neoplasia in semen samples by identification of fetal germ cell-specific markers Hum. Reprod., January 1, 2007; 22(1): 167 - 173. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Houldsworth, J. E. Korkola, G. J. Bosl, and R. S. K. Chaganti Biology and Genetics of Adult Male Germ Cell Tumors J. Clin. Oncol., December 10, 2006; 24(35): 5512 - 5518. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Aflatoonian and H. Moore Germ cells from mouse and human embryonic stem cells. Reproduction, November 1, 2006; 132(5): 699 - 707. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Ferrara, N. Hallmark, H. Scott, R. Brown, C. McKinnell, I. K. Mahood, and R. M. Sharpe Acute and Long-Term Effects of in Utero Exposure of Rats to Di(n-Butyl) Phthalate on Testicular Germ Cell Development and Proliferation Endocrinology, November 1, 2006; 147(11): 5352 - 5362. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Cools, S. L. S. Drop, K. P. Wolffenbuttel, J. W. Oosterhuis, and L. H. J. Looijenga Germ Cell Tumors in the Intersex Gonad: Old Paths, New Directions, Moving Frontiers Endocr. Rev., August 1, 2006; 27(5): 468 - 484. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T.-Y. Ling, M.-D. Kuo, C.-L. Li, A. L. Yu, Y.-H. Huang, T.-J. Wu, Y.-C. Lin, S.-H. Chen, and J. Yu Identification of pulmonary Oct-4+ stem/progenitor cells and demonstration of their susceptibility to SARS coronavirus (SARS-CoV) infection in vitro PNAS, June 20, 2006; 103(25): 9530 - 9535. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Cools, H. Stoop, A.-M. F. Kersemaekers, S. L. S. Drop, K. P. Wolffenbuttel, J.-P. Bourguignon, J. Slowikowska-Hilczer, K. Kula, S. M. H. Faradz, J. W. Oosterhuis, et al. Gonadoblastoma Arising in Undifferentiated Gonadal Tissue within Dysgenetic Gonads J. Clin. Endocrinol. Metab., June 1, 2006; 91(6): 2404 - 2413. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Rajpert-De Meyts Developmental model for the pathogenesis of testicular carcinoma in situ: genetic and environmental aspects Hum. Reprod. Update, May 1, 2006; 12(3): 303 - 323. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Pauls, H. Schorle, W. Jeske, R. Brehm, K. Steger, N. Wernert, R. Buttner, and H. Zhou Spatial expression of germ cell markers during maturation of human fetal male gonads: an immunohistochemical study Hum. Reprod., February 1, 2006; 21(2): 397 - 404. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Sutcliffe, H. A. Spoudeas, D. Nair, P. Bouloux, T. Oliver, P. Sambrook, W. Bannister, C. B. Lambalk, and T. Spector Comparison of serum FSH and Inhibin B levels between adult male dizygotic and monozygotic twins Hum. Reprod., February 1, 2006; 21(2): 447 - 450. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Cools, K. van Aerde, A.-M. Kersemaekers, M. Boter, S. L. S. Drop, K. P. Wolffenbuttel, E. W. Steyerberg, J. W. Oosterhuis, and L. H. J. Looijenga Morphological and Immunohistochemical Differences between Gonadal Maturation Delay and Early Germ Cell Neoplasia in Patients with Undervirilization Syndromes J. Clin. Endocrinol. Metab., September 1, 2005; 90(9): 5295 - 5303. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. E. Hoei-Hansen, E. Rajpert-De Meyts, G. Daugaard, and N. E. Skakkebaek Carcinoma in situ testis, the progenitor of testicular germ cell tumours: a clinical review Ann. Onc., June 1, 2005; 16(6): 863 - 868. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Stoop, F. Honecker, M. Cools, R. de Krijger, C. Bokemeyer, and L.H.J. Looijenga Differentiation and development of human female germ cells during prenatal gonadogenesis: an immunohistochemical study Hum. Reprod., June 1, 2005; 20(6): 1466 - 1476. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. E. Hoei-Hansen, J. E. Nielsen, K. Almstrup, S. B. Sonne, N. Graem, N. E. Skakkebaek, H. Leffers, and E. R.-D. Meyts Transcription Factor AP-2{gamma} Is a Developmentally Regulated Marker of Testicular Carcinoma In situ and Germ Cell Tumors Clin. Cancer Res., December 15, 2004; 10(24): 8521 - 8530. [Abstract] [Full Text] [PDF]
|
|