title: Mitotic arrest in teratoma susceptible fetal male germ cells.
abstract: Formation of germ cell derived teratomas occurs in mice of the 129/SvJ strain, but not in C57Bl/6 inbred or CD1 outbred mice. Despite this, there have been few comparative studies aimed at determining the similarities and differences between teratoma susceptible and non-susceptible mouse strains. This study examines the entry of fetal germ cells into the male pathway and mitotic arrest in 129T2/SvJ mice. We find that although the entry of fetal germ cells into mitotic arrest is similar between 129T2/SvJ, C57Bl/6 and CD1 mice, there were significant differences in the size and germ cell content of the testis cords in these strains. In 129T2/SvJ mice germ cell mitotic arrest involves upregulation of p27(KIP1), p15(INK4B), activation of RB, the expression of male germ cell differentiation markers NANOS2, DNMT3L and MILI and repression of the pluripotency network. The germ-line markers DPPA2 and DPPA4 show reciprocal repression and upregulation, respectively, while FGFR3 is substantially enriched in the nucleus of differentiating male germ cells. Further understanding of fetal male germ cell differentiation promises to provide insight into disorders of the testis and germ cell lineage, such as testis tumour formation and infertility.
authors.affiliation: Centre for Reproduction and Development, Monash Institute of Medical Research, Monash University, Clayton, Victoria, Australia. patrick.western@monash.edu
authors.forename: Patrick S
authors.initials: PS
authors.lastname: Western
authors.forename: Rachael A
authors.initials: RA
authors.lastname: Ralli
authors.forename: Stephanie I
authors.initials: SI
authors.lastname: Wakeling
authors.forename: Camden
authors.initials: C
authors.lastname: Lo
authors.forename: Jocelyn A
authors.initials: JA
authors.lastname: van den Bergen
authors.forename: Denise C
authors.initials: DC
authors.lastname: Miles
authors.forename: Andrew H
authors.initials: AH
authors.lastname: Sinclair
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation; D004198:Disease Susceptibility / Q000378:metabolism / Q000473:pathology; D015536:Down-Regulation; D005333:Fetus / Q000166:cytology* / Q000378:metabolism; D005854:Germ Cells / Q000166:cytology* / Q000378:metabolism; D008297:Male; D051379:Mice; D008938:Mitosis; D009687:Nuclear Proteins / Q000378:metabolism; D050814:Octamer Transcription Factor-3 / Q000378:metabolism; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000378:metabolism; D055748:SOXB1 Transcription Factors / Q000378:metabolism; D013724:Teratoma / Q000473:pathology*; D013737:Testis / Q000166:cytology / Q000378:metabolism; D014157:Transcription Factors
chemical_list: D015415:Biomarkers; C519286:Dppa2 protein, mouse; C519287:Dppa4 protein, mouse; D009687:Nuclear Proteins; D050814:Octamer Transcription Factor-3; C494174:Pou5f1 protein, mouse; D055748:SOXB1 Transcription Factors; C527783:Sox2 protein, mouse; D014157:Transcription Factors; D051498:Receptor, Fibroblast Growth Factor, Type 3