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Hum. Reprod. Advance Access published online on February 25, 2005
Human Reproduction, doi:10.1093/humrep/deh800
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© The Author 2005. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oupjournals.org
Received February 19, 2004
Revised December 24, 2004
Accepted January 20, 2005

Article

Differentiation and development of human female germ cells during prenatal gonadogenesis: an immunohistochemical study

H. Stoop 1, F. Honecker 2, M. Cools 1, R. de Krijger 1, C. Bokemeyer 3, and L.H.J. Looijenga 1*

1 Department of Pathology, Josephine Nefkens Institute, Erasmus MC-University Medical Center Rotterdam, Daniel den Hoed Cancer Center, Rotterdam, The Netherlands
2 Department of Pathology, Josephine Nefkens Institute, Erasmus MC-University Medical Center Rotterdam, Daniel den Hoed Cancer Center, Rotterdam, The Netherlands; Department of Hematology/Oncology, University of Tübingen, Tübingen, Germany
3 Department of Hematology/Oncology, University of Tübingen, Tübingen, Germany

* To whom correspondence should be addressed.
L.H.J. Looijenga, E-mail: l.looijenga{at}erasmusmc.nl


  Abstract

BACKGROUND: In the development of the human ovary, the second trimester includes the transition from oogonial replication to primordial follicle formation. The present study was carried out to assess differentiation and proliferation of germ cells in a series of female gonads from 19 fetuses from the second and third trimester, and two neonates. METHODS: Using immunohistochemistry, the following markers were studied: placental/germ-like cell alkaline phosphatases (PLAP), the marker of pluripotency OCT3/4, the proliferation marker Ki-67, {beta}-catenin and E-cadherin, the stem cell factor receptor c-KIT, and VASA, a protein specific for the germ cell lineage. RESULTS: PLAP and OCT3/4 were seen during oogenesis, but not in germ cells engaged in folliculogenesis. A similar pattern was observed for Ki-67. Loss of pluripotency occurs once oocytes engage in follicle formation, suggesting a role of cell-cell interactions in the process of germ cell maturation. VASA, c-KIT, {beta}-catenin and E-cadherin were found in germ cells at all developmental stages of oogenesis and folliculogenesis. CONCLUSIONS: Immunohistochemically, two groups of germ cells can be distinguished. Germ cells that are predominantly found in the cortical region of the ovary before weeks 22-24 of gestation, showing an immature phenotype, are mitotically active, and express OCT3/4, a marker of pluripotency. On the other hand, germ cells undergoing folliculogenesis have lost their pluripotent potential and no longer proliferate.

Keywords: differentiation; fetal ovary; germ cells; immunohistochemistry; proliferation.
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