Immunohistochemical profiling of germ cells within the human fetal testis: identification of three subpopulations.
In the human fetal testis, germ cells that have migrated to the genital ridges become enclosed within testicular cords by 8 wk of gestation. Most papers refer to all types of germ cells as being "gonocytes" or "prespermatogonia," giving the impression that they are identical. Detailed morphological studies, however, have suggested a heterogeneous population. We have used single, double, and triple immunohistochemistry to evaluate the differentiation of cells within fetal testes recovered during the first (7-9 wk) and second (14-19 wk) trimesters. In the first trimester, differentiation of Sertoli cells preceded the formation of testicular cords and the differentiation of interstitial (Leydig, peritubular myoid) cells. Immunostaining for CHK2, C-KIT, placental alkaline phosphatase, PCTAIRE-1, and MAGE-A4 revealed that the proportion of germ cells expressing each of these proteins was correlated with gestational age. Expression of the pluripotency marker OCT4 was restricted to a population of small, round germ cells. Three types of germ cell were identified, and we propose that these should be known as gonocytes (OCT4pos/C-KITpos/MAGE-A4neg), intermediate germ cells (OCT4low/neg/C-KITneg/MAGE-A4neg), and prespermatogonia (OCT4neg/C-KITneg/MAGE-A4pos). In the first trimester, most germ cells had a gonocyte phenotype; however, from 18 wk of gestation, prespermatogonia were the most abundant cell type. These data provide evidence for the functional differentiation of human testicular germ cells during the second trimester of pregnancy, and they argue against these germ cells being considered as a homogeneous population, as in rodents.
MRC Human Reproductive Sciences Unit, Centre for Reproductive Biology, Edinburgh EH16 4SB, United Kingdom.
Terri L
TL
Gaskell
Arantza
A
Esnal
Lynn L L
LL
Robinson
Richard A
RA
Anderson
Philippa T K
PT
Saunders
D000951:Antigens, Neoplasm; D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000378:metabolism; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009363:Neoplasm Proteins / Q000378:metabolism; D050814:Octamer Transcription Factor-3; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D011262:Pregnancy Trimester, Second; D011506:Proteins / Q000378:metabolism; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D013094:Spermatozoa / Q000145:classification / Q000166:cytology / Q000378:metabolism*; D013737:Testis / Q000196:embryology*; D014157:Transcription Factors / Q000378:metabolism
D000951:Antigens, Neoplasm; D004268:DNA-Binding Proteins; C095204:MAGEA4 protein, human; D009363:Neoplasm Proteins; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; D011506:Proteins; D014157:Transcription Factors; D019009:Proto-Oncogene Proteins c-kit