Germ cells and germ cell transplantation

Abstract

The germ cell lineage in mice is established about a week after fertilization, in a group of cells that have left the epiblast and moved to an extraembryonic site. They migrate back into the embryo, along the hind gut and into the gonads. Germ cells in male and female embryos then pursue different pathways: in the testis the germ cells cease proliferating and enter mitotic arrest, while germ cells in the ovary, like those in male embryos that remain outside the gonads, enter meiotic prophase. Studies on explanted germ cells suggest that all germ cells may enter meiosis at a certain stage of their development, unless prevented from doing so by some inhibitory influence of the testis. Germ cells during the migratory stage can be cultured, but do not enter meiosis unless embedded in somatic tissue. Addition of certain growth factors and cytokines to the culture medium allows germ cells to proliferate indefinitely in vitro: Like embryonic stem cells, these immortalized EG (embryonic germ) cells will colonize all cell lineages if introduced into a blastocyst. After birth, germ cells undergo gametogenesis; oogenesis in the female, spermatogenesis in the male. Brinster and his colleagues have shown that spermatogonial stem cells injected into a germ-cell depleted testis will repopulate the seminiferous tubules and undergo spermatogenesis, giving rise to functional spermatozoa. Stem cells from frozen testicular tissue are still capable of giving rise to spermatogenesis in a host testis. Rat testicular tissue can undergo spermatogenesis in a mouse testis, to form morphologically normal rat spermatozoa, even though the Sertoli cells that support them are of endogenous mouse origin. These findings are of fundamental importance for our understanding of spermatogenesis and the interactions between germ cells and Sertoli cells; but they also have significant practical implications, in relation to both agricultural practice and clinical treatment of infertility.