Origin, Migration, and Proliferation of Human Primordial Germ Cells

Abstract

The fi rst 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 1qEntwick-lungageschichte des Menshen, vol 2. Leipzig, Hirzel, pp 732-955, 1911) were apparently the fi rst 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 identi fi able 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

Evolutionarily diverse mechanisms of germline specification among mammals: what about us?

“…BMP2, BMP4, and WNT3A are expressed at posterior epiblast around the area of PGC specification. The place where human PGCs were identified in the earliest developmental stage of embryos is on the endoderm wall of yolk sac at the angle with allantois around the end of the third week of gestation (7). This is the same place as migrating mouse PGCs are observed.…”

Gonadal development and germ cell tumors in mouse and humans

“…Human PGCs have been also identified by APase staining at around 4 th week of gestation in the wall of the yolk sac and hindgut and move to the GRs by 7 th week (for a review, see [7]) Recent studies have shown similar gene expression patterns in mouse 11.5 dpc and human 7 th -9 th week PGCs. In particular, germline (BLIMP1, AP2γ, UTF1, DAZL, Kit and DDX4) and pluripotency genes (OCT4, NANOG, PRDM14 and LIN28) (Fig.…”

“…Human PGCs proliferate during migration and after GR colonization and a subset of oogonia and gonocytes continues proliferation up to the second trimester of gestation (for a review, see [7]). Several growth factors and cytokines have been reported to affect positively or negatively, the proliferation/survival of mouse PGCs in vitro and/or in vivo.…”

Characteristic Features of Male Germline Development in Primates

“…These data suggest that the ExE is essential for proper PGC specification and development in the mouse. However, since the anatomy and morphology of the mouse and the primate embryo are fundamentally different, with a flat germ disc in primates and an egg cylinder in the mouse [4,33] , there is no direct structural counterpart of the mouse ExE in the primate embryo [34] . Recently, it was shown that the nascent (pregastrulation) amnion is the origin of PGCs in the cynomolgus monkey [13] .…”