Differentiation and development of human female germ cells during prenatal gonadogenesis: an immunohistochemical study.
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.
Stoop
H
H
Department of Pathology, Josephine Nefkens Institute, Erasmus MC-University Medical Center Rotterdam, Rotterdam, The Netherlands.
Honecker
F
F
Cools
M
M
de Krijger
R
R
Bokemeyer
C
C
Looijenga
L H J
LH
D000469:Alkaline Phosphatase / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D003598:Cytoskeletal Proteins / Q000378:metabolism; D053487:DEAD-box RNA Helicases; D004268:DNA-Binding Proteins / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism; D050814:Octamer Transcription Factor-3; D027701:Organic Cation Transport Proteins / Q000378:metabolism; D010053:Ovary / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D010063:Ovum / Q000166:cytology* / Q000502:physiology; D011247:Pregnancy; D011262:Pregnancy Trimester, Second; D011263:Pregnancy Trimester, Third; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D020365:RNA Helicases / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D051176:beta Catenin; D000099254:Organic Cation Transporter 3
D000469:Alkaline Phosphatase; D015415:Biomarkers; D015820:Cadherins; D003598:Cytoskeletal Proteins; D053487:DEAD-box RNA Helicases; D004268:DNA-Binding Proteins; D019394:Ki-67 Antigen; D050814:Octamer Transcription Factor-3; D027701:Organic Cation Transport Proteins; D019009:Proto-Oncogene Proteins c-kit; D020365:RNA Helicases; D015534:Trans-Activators; D014157:Transcription Factors; D051176:beta Catenin; D000099254:Organic Cation Transporter 3; C495270:CTNNB1 protein, human; C494173:POU5F1 protein, human; C498288:DDX4 protein, human