Induction of decidualization of endometrial stromal cells as a therapeutical approach for the treatment of endometriosis
Final Report Abstract
Endometriosis is one of the most common benign gynecological diseases and is associated with pain, subfertility and a severe reduction in quality of life. One cause of endometriosis may be impaired differentiation (decidualization) of endometrial stromal cells (ESCs), possibly due to progesterone resistance. Therefore, in this study, decidualization in ESCs from patients with endometriosis was enhanced by synergistically acting compounds targeting different sites of the decidualization signaling cascade. ESCs were isolated from secretory endometria and incubated in vitro with substances and substance combinations that interact with the progesterone or cAMP signaling pathway. None of the progestins tested alone was able to induce decidualization during the study period. Dezidualization was induced by cAMP and by the adenylate cyclase activator forskolin, but there was no induction by hCG, relaxin, or phosphodiesterase inhibitors alone, which also interact with the cAMP signal cascade. The cAMP effect could be increased by MPA but not by the other progestins tested. In general, the induction of decidualization caused a decrease in cell size and proliferation of ESCs. Interestingly, ESCs from women with endometriosis in trend displayed a stronger resistance to the induction of apoptosis compared to ESCs of endometriosis-free women. This could support the establishment of ectopic endometrial lesions. A significant enhancement of forskolin-induced decidualization was achieved by combined treatment of ESCs with forskolin, phosphodiesterase inhibitors, and MPA. A correlation to steroid hormone receptor expression was observed here to the glucocorticoid receptor rather than the progesterone receptor. By testing the most effective combination of substances in vitro in an in vivo humanized endometriosis mouse model, an incipient decidualization response was seen in the ectopic endometrial lesions after 6 days of treatment. These results may help to develop new therapeutic approaches for the treatment of endometriosis.
Publications
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Effekt der Dezidualisierungs-Induktion auf die Apoptose in ESCs von Patientinnen mit und ohne Endometriose. 18. Treffen des Arbeitskreises Molekularbiologie der DGRM (2018)
Farina Platt, Dunja Baston-Büst, Alexandra Bielfeld & Ruth Grümmer
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Glucocorticoid action in the induction of endometrial stromal cell decidualization. 18. Treffen des Arbeitskreises Molekularbiologie der DGRM (2018)
Aida Nik Bakhsh, Dunja Baston-Büst, Alexandra Bielfeld & Ruth Grümmer
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Human chorionic gonadotropin induces decidualization of ectopic human endometrium more effectively than forskolin in an in-vivo endometriosis model. Experimental Biology and Medicine, 243(11), 953-962.
Koch, Yvonne; Wimberger, Pauline & Grümmer, Ruth
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Optimierung cAMP-vermittelter Signalwege zur Induktion der Dezidualisierung endometrialer Stromazellen bei Patientinnen mit Endometriose. 19. Treffen des Arbeitskreises Molekularbiologie der DGRM (2019)
Janine Moyer, Ines Beyer, Dunja Baston-Büst, Gunther Wennemuth, Alexandra Bielfeld & Ruth Grümmer
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The role of glucocorticoid in endometrial stromal cell (ESCs) decidualization: activation or repression? 19. Treffen des Arbeitskreises Molekularbiologie der DGRM (2019)
Aida Nik Bakhsh, Dunja Baston-Büst, Alexandra Bielfeld & Ruth Grümmer
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Addressing progesterone and cAMP signaling pathways for decidualization induction of endometrial stromal cells of patients with endometriosis. 10th Young Physiologists Symposium (2021)
Janine Moyer, Dunja Baston-Büst, Gunther Wennemuth, Alexandra Bielfeld & Ruth Grümmer
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Addressing progesterone and cAMP signaling pathways for decidualization induction of endometrial stromal cells of patients with endometriosis. 37th Virtual Annual Meeting of ESHRE (2021)
Janine Moyer, Dunja Baston-Büst, Gunther Wennemuth, Alexandra Bielfeld & Ruth Grümmer
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Deutsche Meisterin im Science Slam 2021: Janine Moyer und der Kampf gegen die Endometriose
Moyer, Janine
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Induktion der Dezidualisierung endometrialer Stromazellen: Vergleichende Analysen bei Frauen mit und ohne Endometriose. 20. Treffen des Arbeitskreises Molekularbiologie der DGRM
Janine Moyer, Dunja Baston-Büst, Gunther Wennemuth, Alexandra Bielfeld & Ruth Grümmer
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Optimizing cAMP mediated signaling pathways for decidualization induction of endometrial stromal cells of patients with endometriosis. 14th World Congress on Endometriosis Dubai (2021)
Janine Moyer, Aida Nik Bakhsh, Ines Beyer, Dunja Baston-Büst, Gunther Wennemuth, Alexandra Bielfeld & Ruth Grümmer
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The Role of Glucocorticoids in the Induction of Decidualization of Endometrial Stromal Cells of Women With and Without Endometriosis. Dissertation, Universität Duisburg-Essen.
Nik Bakhsh A.
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Activation of progesterone and cAMP signaling pathways for decidualization induction of endometrial stromal cells of patients with endometriosis. 11th Young Physiologists Symposium (2022)
Janine Moyer, Dunja Baston-Büst, Gunther Wennemuth, Alexandra Bielfeld & Ruth Grümmer
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Untersuchungen zur Induktion der Apoptose bei der Dezidualisierung humaner endometrialer Stromazellen von Patientinnen mit und ohne Endometriose. Dissertation, Universität Duisburg-Essen.
Platt F.
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Einfluss von durch endometriale Epithel- sowie durch Trophoblastzellen sezernierten Faktoren auf die Dezidualisierung humaner endometrialer Stromazellen von Patientinnen mit und ohne Endometriose. Dissertation, Universität Duisburg-Essen.
Schmidt J.
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Enhancing decidualization capacity of endometrial stromal cells of patients with and without endometriosis by addressing progesterone and cAMP signalling pathways. SSR Conference Ottawa (2023)
Janine Moyer, Dunja M. Baston-Buest, Gunther Wennemuth, Alexandra P. Bielfeld & Ruth Grümmer
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Forskolin versus cAMP-Induced Decidualization and Survival of Endometrial Stromal Cells of Endometriosis Patients. Reproductive Sciences, 30(9), 2680-2691.
Platt, Farina; Moyer, Janine; Singer, Bernhard B.; Baston-Büst, Dunja; Wennemuth, Gunther; Bielfeld, Alexandra P. & Grümmer, Ruth
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Induktion der Dezidualisierung endometrialer Stromazellen: Vergleichende Analysen bei Frauen mit und ohne Endometriose. Dissertation, Universität Duisburg-Essen.
Moyer J.
