Int. J. Dev. Biol. 56: 771 - 778 (2012)
doi: 10.1387/ijdb.120202lm
© UPV/EHU Press

The migration and loss of human primordial germ stem cells from the hind gut epithelium towards the gonadal ridge

Linn Salto Mamsen1, Christian Beltoft Brøchner1,2, Anne Grete Byskov1 and Kjeld Møllgard*,2

1Laboratory of Reproductive Biology, The Juliane Marie Centre for Women, Children and Reproduction, University Hospital of Copenhagen, University of Copenhagen, Copenhagen, Denmark and 2 Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences, University of Co-penhagen, Copenhagen, Denmark

ABSTRACT Human primordial germ cells (PGCs) can be recognized in the yolk sac wall, from 3-4 weeks post conception (wpc), in the hind gut epithelium from week 4 and in the gonadal area from early week 5. The objective of this study was to map the migration route of PGCs and elucidate the role of the nervous system in this process. Sixteen human specimens, 5-14 wpc obtained from legal abortions were included. On serial paraffin sections, PGCs were detected immunohistochemically by expression of OCT4 and c-Kit, nerve fibers by β-III-tubulin and stem cell factor (SCF) as a possible chemoattractive cue for PGC migration. PGCs were present in the hind gut epithelium, in the mesenchyme of the dorsal mesentery and in the developing gonadal ridge of 4-6 wpc embryos, prior to connections between the enteric and the sympathetic nervous system. From 6 wpc onwards, the PGCs travelled along the devel-oping nerve fibers from the wall of the hind gut via the dorsal mesentery to the midline of the dorsal wall and laterally into the gonads. Numerous PGCs were still present in the nervous sys-tem by 14 wpc. PGCs in 4-5 wpc embryos are suggested to leave the gut epithelium by EMT-like transition. SCF may facilitate further migration, but after establishment of connections between the enteric and sympathetic nervous systems. PGCs follow sympathetic nerve fibers towards the gonads. PGCs failing to exit the nerve branches at the gonadal site, may continue along the sympathetic trunk ending up in other organs where they may form germ cell tumors if not elimi-nated by apoptosis.

Keywords:

germ cell, migration, nerve fiber, human embryo, first-trimester pregnancy, germ cell tumor

*Corresponding author e-mail: kjm@sund.ku.dk