TY - JOUR

T1 - The migration and loss of human primordial germ stem cells from the hind gut epithelium towards the gonadal ridge

AU - Mamsen, Linn Salto

AU - Brøchner, Christian Beltoft

AU - Byskov, Anne Grete

AU - Møllgård, Kjeld

PY - 2012

Y1 - 2012

N2 - 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 ß-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 developing 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 system 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 eliminated by apoptosis.

AB - 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 ß-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 developing 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 system 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 eliminated by apoptosis.

U2 - 10.1387/ijdb.120202lm

DO - 10.1387/ijdb.120202lm

M3 - Journal article

C2 - 23417399

VL - 56

SP - 771

EP - 778

JO - International Journal of Developmental Biology

JF - International Journal of Developmental Biology

SN - 0214-6282

IS - 10-12

ER -