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. 2004 Nov;5(11):1078-83.
doi: 10.1038/sj.embor.7400279.

Oct4 is required for primordial germ cell survival

James Kehler  1 , Elena Tolkunova, Birgit Koschorz, Maurizio Pesce, Luca Gentile, Michele Boiani, Hilda Lomelí, Andras Nagy, K John McLaughlin, Hans R Schöler, Alexey Tomilin
Affiliations

Oct4 is required for primordial germ cell survival

James Kehler et al. EMBO Rep. 2004 Nov.

Abstract

Previous studies have shown that Oct4 has an essential role in maintaining pluripotency of cells of the inner cell mass (ICM) and embryonic stem cells. However, Oct4 null homozygous embryos die around the time of implantation, thus precluding further analysis of gene function during development. We have used the conditional Cre/loxP gene targeting strategy to assess Oct4 function in primordial germ cells (PGCs). Loss of Oct4 function leads to apoptosis of PGCs rather than to differentiation into a trophectodermal lineage, as has been described for Oct4-deficient ICM cells. These new results suggest a previously unknown function of Oct4 in maintaining viability of mammalian germline.

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Figures

Figure 1
Figure 1
Oct4 phenotype in adult gonads. Immunostaining with Oct-4 antibody (C,D,K,L) and haematoxylin and eosin (A,B,E–J,M) of ovaries of indicated ages (A–H) and 10-week-old testes (I–M), isolated from Δ/Δ (A,C,E,G,I,K,M) and the control group Δ/+ (B,D,F,H,J,L) mice, is shown. The arrows and arrowheads point to primordial (arrows) and growing (arrowheads) follicles in the ovarian sections. In the testicular sections, representative germ-cell-deficient seminiferous tubules are labelled as Δ/Δ and those harbouring normal spermatogenic cells of all stages as Δ/+; the arrowheads point to Oct4-positive spermatogonia type B. Shown are mildly (70%; I,K) and severely (100% of germ-cell-free tubules; M) affected testes. Scale bars in (A) for (A,B,E–M) and in (C) for (C,D) represent 100 μm.
Figure 2
Figure 2
Oct4 phenotype in PGCs. Alkaline phosphatase (AP) staining of Δ/Δ (A,C,E,G,I) and Δ/+ embryos (B,D,F,H,J) is shown. The 8.5 dpc (C,D) and 9.5 dpc (E,F) embryos in both groups show no difference in the number of PGCs (arrows) that are located at the base of allantois within the hindgut pocket (8.5 dpc) and, subsequently, in the hindgut endoderm (9.5 dpc). As opposed to the further increase in the number of PGCs in 10.5 dpc Δ/+ embryos (B,H), the Δ/Δ littermates show a marked decrease in the number of PGCs (A,G), which is further apparent in 12.5 dpc genital ridges (I versus J). Photographs were taken from the ventral (C,D,G,H) or lateral (A,B,E,F) sides of embryos. Scale bars in (C) for (C,D) and in (E) for (E,F) represent 100 μm, and scale bar in (I) for (I,J) represents 200 μm.
Figure 3
Figure 3
Apoptosis of Oct4-deficient PGCs. Labelling with Oct-4 antibody (A,B), and double TUNEL (green)/SSEA-1 antibody (red) staining (C,D) of the Δ/Δ (A,C) and control Δ/+ (B,D) 10.5 dpc embryo sections are shown. Significant reduction in Oct4 protein staining can be seen in the Δ/Δ sections. Shown in (C,D) is the AGM region of the same embryos as in Fig 2G,H. Note a strong TUNEL signal in the nuclei of the same clustered cells showing residual SSEA-1 staining on the cell membrane (C and inset). The SSEA-1 signal was notably weaker than that from viable PGCs of the +/Δ embryos (D) yet sufficiently strong to be distinguished from the background. Scale bars in (A) for (A,B) and in (C) for (C,D) represent 50 μm. The inset is a twofold magnification of the PGC/apoptotic area in (C). Arrowhead, PGC; da, dorsal aorta; dm, dorsal mesentery; gr, genital ridge.
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References

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