Origin, Migration, and Proliferation of Human Primordial Germ Cells

Abstract

The first histological observations about the origin of the precursors of gametes termed primordial germ cells (PGCs) in extragonadal regions and their subsequent migration into the developing gonads in human embryos date back to the early twentieth century. Fuss (Anat Am 39:407–409, 1911, Anat EntwMech 81:1–23, 1912) and Felix (Die Entwicklung der Harn- und Geschlechtsorgane. In: Keibel-Mall Handbuch der 1qEntwicklungageschichte des Menshen, vol 2. Leipzig, Hirzel, pp 732–955, 1911) were apparently the first ones to describe the extragonadal location of PGCs in human embryos. In the youngest, 2.5 mm long, embryo examined (23–26 days postfertilization), These authors described PGCs in the endoderm of the yolk sac wall as cells identifiable by their large size and spherical shape. Subsequently, Politzer (Z Anat Entw Gesch 87: 766–80, 1928, Z Anat Entw Gesch 93:386–428, 1930, Z Anat EntwGesch 100:331–336, 1933) and Witschi (Contr Embryol Carnegie Inst 209:67–80, 1948) ­studied the distribution of PGCs in a considerable number of embryos from presomite stages (0.3–0.8 mm, about 3 weeks) to 8.5 mm (5 weeks). Both authors described the migration of PGCs from the yolk sac to the developing gonads. Following a hot debate, it is now generally accepted that after their arrival into the gonadal anlage, PGCs give rise to the oogonia/oocytes and gonocytes (or prespermatogonia) in the embryonic ovary and testis, respectively. These germ cells enter a complex series of events that in the adult end with the formation of fertilizable oocytes and sperm. Because of the inaccessibility of the human embryo to experimental investigations at these early stages, we still know little about cellular and molecular mechanisms controlling the formation, differentiation, and development of human PGCs. This chapter describes the life history of human PGCs combining old and new information and, where appropriate, making use of the most recent results obtained in the mouse.