Abstract
The leading cause of infertility in men and women is quantitative and qualitative defects in human germ cell (oocyte and sperm) development. Yet, it has been difficult to study human germ cell development, especially features that are unique relative to model organisms. For instance, genes on the sex chromosomes that are commonly deleted in men who make few or no sperm, such as the DAZ (Deleted in AZoospermia) genes, are only present in primates, making functional studies difficult. To probe the unique genetics of germ cell development on a human genome background, we focused on differentiation of human embryonic stem cells (hESCs) to the germ cell lineage. We show that a germ cell reporter can be used to quantitate and isolate primordial germ cells derived from male and female hESCs. Moreover, by silencing and overexpressing specific genes that encode cytoplasmic RNA-binding proteins (not nuclear transcription factors), our results indicate that we can examine and modulate germ cell formation and developmental progression. We observed that the DAZL (Deleted in AZoospermia-Like) gene functions in human primordial germ cell formation, whereas the closely-related family members, DAZ and BOULE, modulate later stages of development including completion of meiosis and development of male gametes. These results are significant to the generation of gametes for future developmental and genetic studies and applications.
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