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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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Morphological and histological analysis of (B6;129) wild-type and K8−/− extraembryonic tissues. Wild-type (A) and K8−/− (B) E10.5 concepti from which the uterine wall and part of decidua are removed. Note the hematoma (h) located between the decidual tissue (dec) and the yolk sac (ys) in the K8−/− conceptus. In mutant conceptus, the placenta (p) is hidden behind the hematoma. (C and D) Sagittal histological sections of E10.5 wild-type (C) and K8−/− (D) concepti. In the wild-type conceptus, the embryo proper (em) is surrounded by the amnion (am), visceral yolk sac (vys), parietal yolk sac (pys), the layer of trophoblast giant cells (arrowheads), and maternal decidual tissue (dec). In the K8−/− conceptus, the hematoma (h) is located between the decidual tissue (dec) and parietal yolk sac (pys). p, placenta. Bar, 200 μm. (E and F) Trophoblast giant cells in E10.5 wild-type (E) and K8−/− (F) concepti at higher magnification. In wild-type conceptus, the continuous layer of trophoblast giant cells (gc) divides maternal decidua (dec) from the parietal yolk sac (pys). Note the disrupted layer of trophoblast giant cells (gc), which undergo degeneration, maternal erythrocytes (er), and fibrin (fb), infiltrated with granulocytes in K8−/− conceptus. Bar, 50 μm.
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fig1: Morphological and histological analysis of (B6;129) wild-type and K8−/− extraembryonic tissues. Wild-type (A) and K8−/− (B) E10.5 concepti from which the uterine wall and part of decidua are removed. Note the hematoma (h) located between the decidual tissue (dec) and the yolk sac (ys) in the K8−/− conceptus. In mutant conceptus, the placenta (p) is hidden behind the hematoma. (C and D) Sagittal histological sections of E10.5 wild-type (C) and K8−/− (D) concepti. In the wild-type conceptus, the embryo proper (em) is surrounded by the amnion (am), visceral yolk sac (vys), parietal yolk sac (pys), the layer of trophoblast giant cells (arrowheads), and maternal decidual tissue (dec). In the K8−/− conceptus, the hematoma (h) is located between the decidual tissue (dec) and parietal yolk sac (pys). p, placenta. Bar, 200 μm. (E and F) Trophoblast giant cells in E10.5 wild-type (E) and K8−/− (F) concepti at higher magnification. In wild-type conceptus, the continuous layer of trophoblast giant cells (gc) divides maternal decidua (dec) from the parietal yolk sac (pys). Note the disrupted layer of trophoblast giant cells (gc), which undergo degeneration, maternal erythrocytes (er), and fibrin (fb), infiltrated with granulocytes in K8−/− conceptus. Bar, 50 μm.

Mentions: The extraembryonic tissues of additional mutant concepti (B6;129) from heterozygous intercrosses were analyzed histologically. Consistent with the functional demonstration that K8−/− embryonic lethality originated from a defect in extraembryonic tissues, the dissection of the uterine wall of heterozygous females revealed partially coagulated blood between the decidua and the yolk sac attached to K8-deficient embryos starting at E10.5. The yolk sac, placenta, and embryo proper appeared normal at this stage (Fig. 1, A and B). Histological examination of five homozygous mutant concepti revealed the presence of massive hemorrhages of maternal blood confined between the decidua capsularis and the parietal yolk sac (Fig. 1, B and D). Resulting hematomas consisted of nonnucleated maternal erythrocytes and fibrin aggregates infiltrated with granulocytes. Hematomas in mutant concepti were apparently due to the disruption of trophoblast giant cell layer (Fig. 1 E) that normally forms a barrier between the maternal and embryonic compartments. At the site of disruption, trophoblast giant cells undergo degeneration (Fig. 1 F). The overall structure of placenta and the yolk sacs in K8−/− concepti (Fig. 1, D and E) and the structure of embryo proper (unpublished data) at E10.5 was morphologically normal.


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)

Morphological and histological analysis of (B6;129) wild-type and K8−/− extraembryonic tissues. Wild-type (A) and K8−/− (B) E10.5 concepti from which the uterine wall and part of decidua are removed. Note the hematoma (h) located between the decidual tissue (dec) and the yolk sac (ys) in the K8−/− conceptus. In mutant conceptus, the placenta (p) is hidden behind the hematoma. (C and D) Sagittal histological sections of E10.5 wild-type (C) and K8−/− (D) concepti. In the wild-type conceptus, the embryo proper (em) is surrounded by the amnion (am), visceral yolk sac (vys), parietal yolk sac (pys), the layer of trophoblast giant cells (arrowheads), and maternal decidual tissue (dec). In the K8−/− conceptus, the hematoma (h) is located between the decidual tissue (dec) and parietal yolk sac (pys). p, placenta. Bar, 200 μm. (E and F) Trophoblast giant cells in E10.5 wild-type (E) and K8−/− (F) concepti at higher magnification. In wild-type conceptus, the continuous layer of trophoblast giant cells (gc) divides maternal decidua (dec) from the parietal yolk sac (pys). Note the disrupted layer of trophoblast giant cells (gc), which undergo degeneration, maternal erythrocytes (er), and fibrin (fb), infiltrated with granulocytes in K8−/− conceptus. Bar, 50 μm.
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fig1: Morphological and histological analysis of (B6;129) wild-type and K8−/− extraembryonic tissues. Wild-type (A) and K8−/− (B) E10.5 concepti from which the uterine wall and part of decidua are removed. Note the hematoma (h) located between the decidual tissue (dec) and the yolk sac (ys) in the K8−/− conceptus. In mutant conceptus, the placenta (p) is hidden behind the hematoma. (C and D) Sagittal histological sections of E10.5 wild-type (C) and K8−/− (D) concepti. In the wild-type conceptus, the embryo proper (em) is surrounded by the amnion (am), visceral yolk sac (vys), parietal yolk sac (pys), the layer of trophoblast giant cells (arrowheads), and maternal decidual tissue (dec). In the K8−/− conceptus, the hematoma (h) is located between the decidual tissue (dec) and parietal yolk sac (pys). p, placenta. Bar, 200 μm. (E and F) Trophoblast giant cells in E10.5 wild-type (E) and K8−/− (F) concepti at higher magnification. In wild-type conceptus, the continuous layer of trophoblast giant cells (gc) divides maternal decidua (dec) from the parietal yolk sac (pys). Note the disrupted layer of trophoblast giant cells (gc), which undergo degeneration, maternal erythrocytes (er), and fibrin (fb), infiltrated with granulocytes in K8−/− conceptus. Bar, 50 μm.
Mentions: The extraembryonic tissues of additional mutant concepti (B6;129) from heterozygous intercrosses were analyzed histologically. Consistent with the functional demonstration that K8−/− embryonic lethality originated from a defect in extraembryonic tissues, the dissection of the uterine wall of heterozygous females revealed partially coagulated blood between the decidua and the yolk sac attached to K8-deficient embryos starting at E10.5. The yolk sac, placenta, and embryo proper appeared normal at this stage (Fig. 1, A and B). Histological examination of five homozygous mutant concepti revealed the presence of massive hemorrhages of maternal blood confined between the decidua capsularis and the parietal yolk sac (Fig. 1, B and D). Resulting hematomas consisted of nonnucleated maternal erythrocytes and fibrin aggregates infiltrated with granulocytes. Hematomas in mutant concepti were apparently due to the disruption of trophoblast giant cell layer (Fig. 1 E) that normally forms a barrier between the maternal and embryonic compartments. At the site of disruption, trophoblast giant cells undergo degeneration (Fig. 1 F). The overall structure of placenta and the yolk sacs in K8−/− concepti (Fig. 1, D and E) and the structure of embryo proper (unpublished data) at E10.5 was morphologically normal.

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