title: Perinatal germ cell development and differentiation in the male marmoset (Callithrix jacchus): similarities with the human and differences from the rat.
abstract: OBJECTIVE
  Is perinatal germ cell (GC) differentiation in the marmoset similar to that in the human?
  
  
  CONCLUSIONS
  In a process comparable with the human, marmoset GC differentiate rapidly after birth, losing OCT4 expression after 5-7 weeks of age during mini-puberty.
  
  
  BACKGROUND
  Most of our understanding about perinatal GC development derives from rodents, in which all gonocytes (undifferentiated GC) co-ordinately lose expression of the pluripotency factor OCT4 and stop proliferating in late gestation. Then after birth these differentiated GC migrate to the basal lamina and resume proliferation prior to the onset of spermatogenesis. In humans, fetal GC differentiation occurs gradually and asynchronously and OCT4(+) GC persist into perinatal life. Failure to switch off OCT4 in GC perinatally can lead to development of carcinoma in situ (CIS), the precursor of testicular germ cell cancer (TGCC), for which there is no animal model. Marmosets show similarities to the human, but systematic evaluation of perinatal GC development in this species is lacking. Similarity, especially for loss of OCT4 expression, would support use of the marmoset as a model for the human and for studying CIS origins.
  
  
  METHODS
  Testis tissues were obtained from marmosets (n = 4-10 per age) at 12-17 weeks' gestation and post-natal weeks 0.5, 2.5, 5-7, 14 and 22 weeks, humans at 15-18 weeks' gestation (n = 5) and 4-5 weeks of age (n = 4) and rats at embryonic day 21.5 (e21.5) (n = 3) and post-natal days 4, 6 and 8 (n = 4 each).
  
  
  METHODS
  Testis sections from fetal and post-natal marmosets, humans and rats were collected and immunostained for OCT4 and VASA to identify undifferentiated and differentiated GC, respectively, and for Ki67, to identify proliferating GC. Stereological quantification of GC numbers, differentiation (% OCT4(+) GC) and proliferation were performed in perinatal marmosets and humans. Quantification of GC position within seminiferous cords was performed in marmosets, humans and rats.
  
  
  RESULTS
  The total GC number increased 17-fold from birth to 22 post-natal weeks in marmosets; OCT4(+) and VASA(+) GC proliferated equally in late gestation and early post-natal life. The percentage of OCT4(+) GC fell from 54% in late fetal life to <0.5% at 2.5 weeks of age and none were detected after 5-7 weeks in marmosets. In humans, the percentage of OCT4(+) GC also declined markedly during the equivalent period. In marmosets, GC had begun migrating to the base of seminiferous cords at ∼22 weeks of age, after the loss of GC OCT4 expression.
  
  
  CONCLUSIONS
  There is considerable individual variation between marmosets. Although GC development in marmosets and humans was similar, there are differences with respect to proliferation during fetal life. The number of human samples was limited.
  
  
  CONCLUSIONS
  The similarities in testicular GC differentiation between marmosets and humans during the perinatal period, and their differences from rodents, suggest that the marmoset may be a useful model for studying the origins of CIS, with relevance for the study of TGCC.
  
  
  BACKGROUND
  This work was supported by Grant G33253 from the Medical Research Council, UK. No external funding was sought and there are no competing interests.
authors: MRC/University of Edinburgh Centre for Reproductive Health, The Queen's Medical Research Institute, Edinburgh, UK. c.mckinnell@ed.ac.uk
authors: Chris
authors: C
authors: McKinnell
authors: Rod T
authors: RT
authors: Mitchell
authors: Keith
authors: K
authors: Morris
authors: Richard A
authors: RA
authors: Anderson
authors: Chris J H
authors: CJ
authors: Kelnar
authors: W Hamish
authors: WH
authors: Wallace
authors: Richard M
authors: RM
authors: Sharpe
mesh_terms: D000818:Animals; D002144:Callithrix / Q000502:physiology*; D002278:Carcinoma in Situ / Q000473:pathology; D002454:Cell Differentiation; D049109:Cell Proliferation; D004195:Disease Models, Animal; D006801:Humans; D008297:Male; D050810:Octamer Transcription Factors / Q000235:genetics / Q000378:metabolism; D051381:Rats; D013094:Spermatozoa / Q000166:cytology*; D013737:Testis / Q000166:cytology / Q000378:metabolism / Q000473:pathology
chemical_list: D050810:Octamer Transcription Factors