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Keratin 8 protection of placental barrier function.

Jaquemar D, Kupriyanov S, Wankell M, Avis J, Benirschke K, Baribault H, Oshima RG - J. Cell Biol. (2003)

Bottom Line: The ConA-induced failure of the trophoblast giant cell barrier results in hematoma formation between the trophoblast giant cell layer and the embryonic yolk sac in a phenocopy of dying K8-deficient concepti in a sensitive genetic background.We conclude the lethality of K8-/- embryos is due to a TNF-sensitive failure of trophoblast giant cell barrier function.The keratin-dependent protection of trophoblast giant cells from a maternal TNF-dependent apoptotic challenge may be a key function of simple epithelial keratins.

View Article: PubMed Central - PubMed

Affiliation: The Burnham Institute, La Jolla, CA 92037, USA.

ABSTRACT
The intermediate filament protein keratin 8 (K8) is critical for the development of most mouse embryos beyond midgestation. We find that 68% of K8-/- embryos, in a sensitive genetic background, are rescued from placental bleeding and subsequent death by cellular complementation with wild-type tetraploid extraembryonic cells. This indicates that the primary defect responsible for K8-/- lethality is trophoblast giant cell layer failure. Furthermore, the genetic absence of maternal but not paternal TNF doubles the number of viable K8-/- embryos. Finally, we show that K8-/- concepti are more sensitive to a TNF-dependent epithelial apoptosis induced by the administration of concanavalin A (ConA) to pregnant mothers. The ConA-induced failure of the trophoblast giant cell barrier results in hematoma formation between the trophoblast giant cell layer and the embryonic yolk sac in a phenocopy of dying K8-deficient concepti in a sensitive genetic background. We conclude the lethality of K8-/- embryos is due to a TNF-sensitive failure of trophoblast giant cell barrier function. The keratin-dependent protection of trophoblast giant cells from a maternal TNF-dependent apoptotic challenge may be a key function of simple epithelial keratins.

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Apoptotic trophoblast giant cells in ConA-treated mice. Sections of the placenta (A and B) and uterine wall (C–F) were stained for K8 (A and B) and apoptotic nuclei by the TUNEL method (C–E). F shows a neighboring section of E stained with hematoxylin and eosin. Tissues with K8−/− concepti are shown in B–F. The tissues are labeled: d, decidua; eb, embryonic blood; gtc, giant trophoblast cell; h, hemorrhage; L, labyrinth region; stc, spongiotrophoblast cell; r, Reicharts membrane; ys, yolk sac. The black arrows in C–F indicate apoptotic giant cells. Bar, 100 μm. The tissue shown in E and F represent an adjacent uterine wall region which has folded up against the placental region as revealed by tracing the folded yolk sac basement membrane. This results in the atypical juxtaposition of the failed trophoblast giant cell layer against the labyrinth region of the placenta. Note the apoptotic giant cell nuclei associate with the accumulated hematomas.
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fig6: Apoptotic trophoblast giant cells in ConA-treated mice. Sections of the placenta (A and B) and uterine wall (C–F) were stained for K8 (A and B) and apoptotic nuclei by the TUNEL method (C–E). F shows a neighboring section of E stained with hematoxylin and eosin. Tissues with K8−/− concepti are shown in B–F. The tissues are labeled: d, decidua; eb, embryonic blood; gtc, giant trophoblast cell; h, hemorrhage; L, labyrinth region; stc, spongiotrophoblast cell; r, Reicharts membrane; ys, yolk sac. The black arrows in C–F indicate apoptotic giant cells. Bar, 100 μm. The tissue shown in E and F represent an adjacent uterine wall region which has folded up against the placental region as revealed by tracing the folded yolk sac basement membrane. This results in the atypical juxtaposition of the failed trophoblast giant cell layer against the labyrinth region of the placenta. Note the apoptotic giant cell nuclei associate with the accumulated hematomas.

Mentions: Immunohistochemical analysis of extraembryonic tissues of ConA-treated mice confirmed the expression of K8 in trophoblast derivatives, including spongiotrophoblast, giant cells, and epithelial cells, in the labyrinth region recognized by the presence of nucleated embryonic blood cells (Fig. 6 A). The placentas of E10 K8−/− embryos had a relatively normal structure but lacked K8 (Fig. 6 B). Staining nuclei for DNA nicks by the TUNEL method revealed apoptotic and degenerating giant cells near the large hematomas (Fig. 6, C–F). However, apoptotic giant cells were found in both K8+/− and K8−/− implantation sites, and it was not possible to distinguish the genotype based solely on apoptotic staining because of the relatively late stage at which hematoma formation best distinguished the K8-positive and -negative concepti. Nevertheless, these results confirmed apoptotic giant cells are common in ConA-treated mothers by the time large hematomas are detected.


Keratin 8 protection of placental barrier function.

Jaquemar D, Kupriyanov S, Wankell M, Avis J, Benirschke K, Baribault H, Oshima RG - J. Cell Biol. (2003)

Apoptotic trophoblast giant cells in ConA-treated mice. Sections of the placenta (A and B) and uterine wall (C–F) were stained for K8 (A and B) and apoptotic nuclei by the TUNEL method (C–E). F shows a neighboring section of E stained with hematoxylin and eosin. Tissues with K8−/− concepti are shown in B–F. The tissues are labeled: d, decidua; eb, embryonic blood; gtc, giant trophoblast cell; h, hemorrhage; L, labyrinth region; stc, spongiotrophoblast cell; r, Reicharts membrane; ys, yolk sac. The black arrows in C–F indicate apoptotic giant cells. Bar, 100 μm. The tissue shown in E and F represent an adjacent uterine wall region which has folded up against the placental region as revealed by tracing the folded yolk sac basement membrane. This results in the atypical juxtaposition of the failed trophoblast giant cell layer against the labyrinth region of the placenta. Note the apoptotic giant cell nuclei associate with the accumulated hematomas.
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Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2199358&req=5

fig6: Apoptotic trophoblast giant cells in ConA-treated mice. Sections of the placenta (A and B) and uterine wall (C–F) were stained for K8 (A and B) and apoptotic nuclei by the TUNEL method (C–E). F shows a neighboring section of E stained with hematoxylin and eosin. Tissues with K8−/− concepti are shown in B–F. The tissues are labeled: d, decidua; eb, embryonic blood; gtc, giant trophoblast cell; h, hemorrhage; L, labyrinth region; stc, spongiotrophoblast cell; r, Reicharts membrane; ys, yolk sac. The black arrows in C–F indicate apoptotic giant cells. Bar, 100 μm. The tissue shown in E and F represent an adjacent uterine wall region which has folded up against the placental region as revealed by tracing the folded yolk sac basement membrane. This results in the atypical juxtaposition of the failed trophoblast giant cell layer against the labyrinth region of the placenta. Note the apoptotic giant cell nuclei associate with the accumulated hematomas.
Mentions: Immunohistochemical analysis of extraembryonic tissues of ConA-treated mice confirmed the expression of K8 in trophoblast derivatives, including spongiotrophoblast, giant cells, and epithelial cells, in the labyrinth region recognized by the presence of nucleated embryonic blood cells (Fig. 6 A). The placentas of E10 K8−/− embryos had a relatively normal structure but lacked K8 (Fig. 6 B). Staining nuclei for DNA nicks by the TUNEL method revealed apoptotic and degenerating giant cells near the large hematomas (Fig. 6, C–F). However, apoptotic giant cells were found in both K8+/− and K8−/− implantation sites, and it was not possible to distinguish the genotype based solely on apoptotic staining because of the relatively late stage at which hematoma formation best distinguished the K8-positive and -negative concepti. Nevertheless, these results confirmed apoptotic giant cells are common in ConA-treated mothers by the time large hematomas are detected.

Bottom Line: The ConA-induced failure of the trophoblast giant cell barrier results in hematoma formation between the trophoblast giant cell layer and the embryonic yolk sac in a phenocopy of dying K8-deficient concepti in a sensitive genetic background.We conclude the lethality of K8-/- embryos is due to a TNF-sensitive failure of trophoblast giant cell barrier function.The keratin-dependent protection of trophoblast giant cells from a maternal TNF-dependent apoptotic challenge may be a key function of simple epithelial keratins.

View Article: PubMed Central - PubMed

Affiliation: The Burnham Institute, La Jolla, CA 92037, USA.

ABSTRACT
The intermediate filament protein keratin 8 (K8) is critical for the development of most mouse embryos beyond midgestation. We find that 68% of K8-/- embryos, in a sensitive genetic background, are rescued from placental bleeding and subsequent death by cellular complementation with wild-type tetraploid extraembryonic cells. This indicates that the primary defect responsible for K8-/- lethality is trophoblast giant cell layer failure. Furthermore, the genetic absence of maternal but not paternal TNF doubles the number of viable K8-/- embryos. Finally, we show that K8-/- concepti are more sensitive to a TNF-dependent epithelial apoptosis induced by the administration of concanavalin A (ConA) to pregnant mothers. The ConA-induced failure of the trophoblast giant cell barrier results in hematoma formation between the trophoblast giant cell layer and the embryonic yolk sac in a phenocopy of dying K8-deficient concepti in a sensitive genetic background. We conclude the lethality of K8-/- embryos is due to a TNF-sensitive failure of trophoblast giant cell barrier function. The keratin-dependent protection of trophoblast giant cells from a maternal TNF-dependent apoptotic challenge may be a key function of simple epithelial keratins.

Show MeSH
Related in: MedlinePlus