In vivo and in vitro differentiation of male germ cells in the mouse

Abstract

Primordial germ cells appear in the embryo at about day 7 after coitum. They proliferate and migrate towards the genital ridge. Once there, they undergo differentiation into germ stem cells, known as 'A spermatogonia'. These cells are the foundation of spermatogenesis. A spermatogonia commit to spermatogenesis, stay undifferentiated or degenerate. The differentiation of primordial germ cells to migratory, postmigratory and germ stem cells is dependent on gene expression and cellular interactions. Some of the genes that play a crucial role in germ cell differentiation are Steel, c-Kit, VASA, DAZL, fragilis, miwi, mili, mil1 and mil2. Their expression is stage specific, therefore allowing solid identification of germ cells at different developmental phases. In addition to the expression of these genes, other markers associated with germ cell development are nonspecific alkaline phosphatase activity, the stage specific embryonic antigen, the transcription factor Oct3/4 and b1-and a6-integrins. Commitment of cells to primordial germ cells and to A spermatogonia is also dependent on induction by the bone morphogenetic protein (BMP)-4. With this knowledge, researchers were able to isolate germ stem cells from embryonic stem cell-derived embryoid bodies, and drive these into gametes either in vivo or in vitro. Although no viable embryos were obtained from these gametes, the prospects are that this goal is not too far from being accomplished.

Derivation of male germ cells from bone marrow stem cells

“…8 Loss of Mvh function causes a deficiency in the proliferation and differentiation of male germ cells. 22 These results indicate that a subpopulation of BSCderived cells can be characterized as PGCs.…”

“…Furthermore, we used RT-PCR to detect expression of fragilis, stella, Mvh; and Rnf17 genes, which are expressed in early stage of male germ cell development. [6][7][8]22 All four genes were expressed in BMS-GC, but not in untreated BMS (Figure 4). Fragilis is the first gene to mark the onset of germ cell competence, and it follows Differentiation of MSC to male germ cells K Nayernia et al a pattern consistent with the eventual segregation of germ cells from allantoic precursors.…”

How to Preserve Fertility in Young Women Exposed to Chemotherapy? The Role of GnRH Agonist Cotreatment in Addition to Cryopreservation of Embrya, Oocytes, or Ovaries

“…These observations are in contrast to the older assumption that early follicles are completely gonadotropin independent [51]. Furthermore, two recent publications found that the proliferation of primordial germ cells is gonadotropin dependent and is mediated by Akt/phosphatase and tensin homologue deleted on chromosome ten (PTEN) signaling [54,55]. High concentrations of estrogens stimulate mouse primordial germ cell growth in vitro through the somatic cells of the gonad [54,55].…”

Testicular germ cells can colonize sexually undifferentiated embryonic gonad and produce functional eggs in fish

“…Morphologically, spermatogonial stem cells are smaller than their sexually undifferentiated progenitor PGCs and possess distinctive microstructures (7). Furthermore, the differentiation of mouse PGCs into spermatogonial stem cells alters the expression of various genes, including alkaline phosphatase, c-kit (8), nanos homologue 2 (nanos2), and nanos homologue 3 (nanos3) (9). Yet it remains unclear how these shifts in gene expression induce functional differences between vertebrate PGCs and spermatogonial stem cells.…”