Primordial germ cells (PGCs) are the precursors of gametes that are unipotent and differentiate into sperm and oocytes. PGCs originate in the endodermal epithelium of the yolk sac in human embryos and migrate to the developing gonads guided by chemical signals. They are specified through a transcription factor network including BMP4 and PRDM14 that allows them to regain pluripotency. In the developing gonads, the sex chromosomes determine if the gonad develops as a testis or ovary, influencing if the PGCs become oocytes or gonocytes that later develop into sperm.

1. PRIMORDIAL GERM CELLS
M. VharshiniM. Vharshini
MSc 1MSc 1stst
yearyear
Roll No.: 35Roll No.: 35

2. Introduction
• Primordial germ cells (PGCs) are the precursors of the gametes.
• They are unipotent and differentiate into sperm and oocytes.
• PGCs in culture can give rise to pluripotent embryonic stem cells.
• PGCs in are extensively studied in models like drosophila, zebrafish,
mice but human are not well studied due to ethical issues
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3. Time line of PGCs in Mouse and
Human
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4. • PGCs are generally
 Spherical and larger in size,
 large nucleus with marked nuclear membrane.
 have high electron cytoplasm density and irregular outline
• Diameter: 10 - 20 µm.
• “Nuage material" is a conserved feature of germ
cell; appears as electron-dense granules and
localized to cytoplasmic phase of the nuclear
envelope.
• Morphological modifications of PGCs depending
on the phase:
– Separation & Migration PhaseSeparation & Migration Phase – Ameoboid shape ;
nucleus attains irregular contour.
– Colonization PhaseColonization Phase – Round or elliptical
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Fig1: PGC (chicken)
scanning electron
micrograph.
Morphology
Fig 2: PGC. nucleus (n),
cytoplasm (sit), mitochondria
(m), nuage material (arrow).

5. • PGCs are stained more densely than somatic cells.
• Peripheral cytoplasm shows high alkaline phosphatase
(AP) activity – Marker
• The "nuage material" has electron-dense granules
give positivepositive reactionreaction with H&E staining.
• VasaVasa and nanosnanos genes can be used as molecular marker.
• Currently PGCs are most identified by using the monoclonal
antibodies such as stage-specific embryonic antigens α-SSEA-
1, α-SSEA-3, SSEA-4.
• α-SSEA-1 is the most widely used marker for PGCs.
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Histological and Immunohistochemical
Identification
Fig3: α-SSEA-1
positive PGCs

6. Origin
• In mammals the primordial germ cells
have extra-gonadal origin.
• Alkaline phosphatase enzyme is used as a
marker to determine the location and
migration of these cells.
• In human embryo, PGCs originate in the
endodermal epitheliumendodermal epithelium of the yolk sac in
the vicinity of the allantoic stalkallantoic stalk.
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7. Specification
• PGCs arise at the onset of gastrulation through a process
of inductive signaling.
• Bone morphogenetic protein 4 (BMP4) fragilis
• The PGC competent proximal epiblast cells expressing
fragilisfragilis are initially destined for a somatic fatesomatic fate.
• Also there is up-regulation of Sox2, Nanog genes re-
expressed in PGCs pluripotency.
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Neighboring
somatic cells
Precursor
PGCs
PGCs in
extra-gonadal
region
Commitment
Specification
Signals
Induce
Re-gain

8. Specification-Tripartite transcription factor
network
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Prdm14
Blimp1
Tcfap2c
Germ Cell Gene
Expression
Germ Cell Migration
Somatic Cell Gene
Expression
Tripartitetranscriptionfactornetwork

9. Migration
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•Begins to migrate from yolk sac in the 4th
week and reached gonads by 5th
week
in mammals.
•Controlled through two separate ligand-receptor chemo-attractant signaling
interactions.

10. Migration
• The GR secretes stromal cell-derived
factor1 (SDF1) provides directional cue for
PGC.
• Germ cells lacking the SDF1 receptor fail to
colonise the gonads efficiently
• Alkaline phosphatase enzyme is used as a
marker to identify the migration path.
• Genetic reprogramming, DNA methylation,
erasure of gene imprinting occurs during
migration.
• By default, bipotenital gonad produces
female reproductive organs, unless male-
specific factors are upregulated.
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• The sex chromosomes in the
somatic cells of the genital ridge
determine which type of gonad
the ridge becomes.
• In females:In females:
PGCs Oogonia
• Oogonia gets arrested at diplotene
stage in Meiosis1.
• In the male, after reaching the
developing testis, PGCs are
usually termed gonocytes.
• Gonocytes enter mitotic arrest
and stay quiescent till birth.
Sex differentiation
Differentiates
9th
wk

12. SRY gene
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13. THANK YOU
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