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Apoptosis in uterine epithelium and decidua in response to implantation: evidence for two different pathways.

Joswig A, Gabriel HD, Kibschull M, Winterhager E - Reprod. Biol. Endocrinol. (2003)

Bottom Line: Strong immunolabelling for the initiator caspase-9 was restricted to the decidual compartment, whereas caspase-3 expression characterized the apoptotic uterine epithelium.Only some caspase-3 positive decidual cells were found around the embryo which correlated to the pattern of Tunel staining.Taken together, the apoptotic degeneration of the uterine epithelium seems to be mediated by TNF receptor1 followed by caspase-3, whereas the very moderate regression of the decidua did not show the investigated death receptor, but Bax and Blc2 instead and in addition caspase-9, which indicates a different regulation for epithelial versus decidual apoptosis.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute of Anatomy, University Hospital of Essen, Essen, Germany. ajoswig@yahoo.com

ABSTRACT
During the initial steps of implantation, the mouse uterine epithelium of the implantation chamber undergoes apoptosis in response to the interacting blastocyst. With progressing implantation, regression of the decidual cells allows a restricted and coordinated invasion of trophoblast cells into the maternal compartment. In order to investigate pathways of apoptosis in mouse uterine epithelium and decidua during early pregnancy (day 4.5-7.0 post coitum), we have investigated different proteins such as TNFalpha, TNF receptor1, Fas ligand, Fas receptor1, Bax and Bcl2 as well as caspase-9 and caspase-3 using immunohistochemistry. To detect cells undergoing apoptosis the Tunel assay was performed. Immunoreactivity for TNFalpha as well as for TNF receptor1 was observed exclusively in the epithelium of the implantation chamber and the adjacent luminal epithelium from day 4.5 post coitum onwards. In the developing decidua the Fas ligand, but not the Fas receptor, was expressed. Bax and Bcl2 revealed a complementary expression pattern with Bax in the primary and Bcl2 in the adjacent decidual zone. Strong immunolabelling for the initiator caspase-9 was restricted to the decidual compartment, whereas caspase-3 expression characterized the apoptotic uterine epithelium. Only some caspase-3 positive decidual cells were found around the embryo which correlated to the pattern of Tunel staining. Taken together, the apoptotic degeneration of the uterine epithelium seems to be mediated by TNF receptor1 followed by caspase-3, whereas the very moderate regression of the decidua did not show the investigated death receptor, but Bax and Blc2 instead and in addition caspase-9, which indicates a different regulation for epithelial versus decidual apoptosis.

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Immunostaining for Bax/Bcl2 Bax reveals weak expression in the developing decidua, but not in the uterine epithelium of the implantation chamber on 4.5 dpc (a). At the same stage Bcl2 is not expressed in the primary decidual zone, but in the surrounding stroma (b). On day 6.5 pc distribution of Bax is predominantly observed in the antimesometrial decidua up to the myometrial layers, whereas the mesometrial side is only weakly stained (c). IC, implantation chamber; E, luminal uterine epithelium; m, mesometrial side; am, antimesometrial side; PD, primary decidual zone, M, myometrium. Bar represents 100 μm in a, b and 500 μm in c.
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Figure 3: Immunostaining for Bax/Bcl2 Bax reveals weak expression in the developing decidua, but not in the uterine epithelium of the implantation chamber on 4.5 dpc (a). At the same stage Bcl2 is not expressed in the primary decidual zone, but in the surrounding stroma (b). On day 6.5 pc distribution of Bax is predominantly observed in the antimesometrial decidua up to the myometrial layers, whereas the mesometrial side is only weakly stained (c). IC, implantation chamber; E, luminal uterine epithelium; m, mesometrial side; am, antimesometrial side; PD, primary decidual zone, M, myometrium. Bar represents 100 μm in a, b and 500 μm in c.

Mentions: Bax and Bcl2 are well known counterplayers which regulate apoptosis. Immunostaining for Bax and Bcl2 was not observed in the endometrium of nonpregnant animals and during the preimplantation phase. At implantation Bax and Bcl2 exhibited complementary expression patterns. At day 4.5 pc the pro-apoptotic Bax protein showed restricted labelling in the primary decidual zone around the implanting embryo (Fig. 3a). This expression was enhanced and spread out from the primary decidual zone (data not shown). On day 6.5 pc Bax staining was seen throughout the whole antimesometrial decidua up to the myometrial wall, and Bax expression started at the mesometrial side (Fig. 3c). In contrast Bcl2 was not expressed in the primary decidual zone on day 4.5 pc (Fig. 3b) until day 6.5 pc, but was observed in the adjacent stroma. Its expression decreased from day 6.5 pc onwards (data not shown). Both proteins were not detectable in the uterine epithelial compartment (see Fig. 3a for Bax and Fig. 3b for Bcl2).


Apoptosis in uterine epithelium and decidua in response to implantation: evidence for two different pathways.

Joswig A, Gabriel HD, Kibschull M, Winterhager E - Reprod. Biol. Endocrinol. (2003)

Immunostaining for Bax/Bcl2 Bax reveals weak expression in the developing decidua, but not in the uterine epithelium of the implantation chamber on 4.5 dpc (a). At the same stage Bcl2 is not expressed in the primary decidual zone, but in the surrounding stroma (b). On day 6.5 pc distribution of Bax is predominantly observed in the antimesometrial decidua up to the myometrial layers, whereas the mesometrial side is only weakly stained (c). IC, implantation chamber; E, luminal uterine epithelium; m, mesometrial side; am, antimesometrial side; PD, primary decidual zone, M, myometrium. Bar represents 100 μm in a, b and 500 μm in c.
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Related In: Results  -  Collection

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Figure 3: Immunostaining for Bax/Bcl2 Bax reveals weak expression in the developing decidua, but not in the uterine epithelium of the implantation chamber on 4.5 dpc (a). At the same stage Bcl2 is not expressed in the primary decidual zone, but in the surrounding stroma (b). On day 6.5 pc distribution of Bax is predominantly observed in the antimesometrial decidua up to the myometrial layers, whereas the mesometrial side is only weakly stained (c). IC, implantation chamber; E, luminal uterine epithelium; m, mesometrial side; am, antimesometrial side; PD, primary decidual zone, M, myometrium. Bar represents 100 μm in a, b and 500 μm in c.
Mentions: Bax and Bcl2 are well known counterplayers which regulate apoptosis. Immunostaining for Bax and Bcl2 was not observed in the endometrium of nonpregnant animals and during the preimplantation phase. At implantation Bax and Bcl2 exhibited complementary expression patterns. At day 4.5 pc the pro-apoptotic Bax protein showed restricted labelling in the primary decidual zone around the implanting embryo (Fig. 3a). This expression was enhanced and spread out from the primary decidual zone (data not shown). On day 6.5 pc Bax staining was seen throughout the whole antimesometrial decidua up to the myometrial wall, and Bax expression started at the mesometrial side (Fig. 3c). In contrast Bcl2 was not expressed in the primary decidual zone on day 4.5 pc (Fig. 3b) until day 6.5 pc, but was observed in the adjacent stroma. Its expression decreased from day 6.5 pc onwards (data not shown). Both proteins were not detectable in the uterine epithelial compartment (see Fig. 3a for Bax and Fig. 3b for Bcl2).

Bottom Line: Strong immunolabelling for the initiator caspase-9 was restricted to the decidual compartment, whereas caspase-3 expression characterized the apoptotic uterine epithelium.Only some caspase-3 positive decidual cells were found around the embryo which correlated to the pattern of Tunel staining.Taken together, the apoptotic degeneration of the uterine epithelium seems to be mediated by TNF receptor1 followed by caspase-3, whereas the very moderate regression of the decidua did not show the investigated death receptor, but Bax and Blc2 instead and in addition caspase-9, which indicates a different regulation for epithelial versus decidual apoptosis.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute of Anatomy, University Hospital of Essen, Essen, Germany. ajoswig@yahoo.com

ABSTRACT
During the initial steps of implantation, the mouse uterine epithelium of the implantation chamber undergoes apoptosis in response to the interacting blastocyst. With progressing implantation, regression of the decidual cells allows a restricted and coordinated invasion of trophoblast cells into the maternal compartment. In order to investigate pathways of apoptosis in mouse uterine epithelium and decidua during early pregnancy (day 4.5-7.0 post coitum), we have investigated different proteins such as TNFalpha, TNF receptor1, Fas ligand, Fas receptor1, Bax and Bcl2 as well as caspase-9 and caspase-3 using immunohistochemistry. To detect cells undergoing apoptosis the Tunel assay was performed. Immunoreactivity for TNFalpha as well as for TNF receptor1 was observed exclusively in the epithelium of the implantation chamber and the adjacent luminal epithelium from day 4.5 post coitum onwards. In the developing decidua the Fas ligand, but not the Fas receptor, was expressed. Bax and Bcl2 revealed a complementary expression pattern with Bax in the primary and Bcl2 in the adjacent decidual zone. Strong immunolabelling for the initiator caspase-9 was restricted to the decidual compartment, whereas caspase-3 expression characterized the apoptotic uterine epithelium. Only some caspase-3 positive decidual cells were found around the embryo which correlated to the pattern of Tunel staining. Taken together, the apoptotic degeneration of the uterine epithelium seems to be mediated by TNF receptor1 followed by caspase-3, whereas the very moderate regression of the decidua did not show the investigated death receptor, but Bax and Blc2 instead and in addition caspase-9, which indicates a different regulation for epithelial versus decidual apoptosis.

Show MeSH
Related in: MedlinePlus