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 p27KIP1, p15INK4B, 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.
Highlights
Development of the spermatogenic and oogenic lineages is initiated from bi-potential primordial germ cells in the midgestation mouse fetus
We examined the expression of NANOS2, MILI and DNMT3L, which are involved in fetal male germ cell development [26,27,28,33,34,35,36]
In 129/SvJ mice the fetal male germ cells are susceptible to forming teratomas at E12.5, this susceptibility is rapidly lost during E13.5 and E14.5, implying that entry into the male developmental pathway and mitotic arrest is important in delivering tumour resistance
Summary
Development of the spermatogenic and oogenic lineages is initiated from bi-potential primordial germ cells in the midgestation mouse fetus. Commitment to male or female germ cell development is dependant not on the chromosomal sex of the germ cells, but on the surrounding gonadal cell environment indicating that intercellular signalling plays a central role in this process (For reviews see [1,2,3,4]). Commitment of the germ cells to male development occurs by E12.5 and results in a period of mitotic quiescence. The male germ cells re-enter the cell cycle post-natally and undergo a highly regulated phase of spermatogenic differentiation. Female germ cell commitment occurs at E13.5 and the developing oocytes immediately enter the meiotic program, arrest in diplotene at birth and complete meiosis during oocyte maturation [5]. Recent studies question the role of RA in these processes [12,13]
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