Progesterone-independent induction of decidualization of endometrial stromal cells of patients with and without endometriosis

In: Geburtshilfe und Frauenheilkunde · 2015 · vol. 75(07) · doi:10.1055/s-0035-1558381 · W2616590047
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This study investigated whether endometrial stromal cells from endometriosis patients could be decidualized without progesterone receptor activation.

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This study investigated whether decidualization could be induced in endometrial stromal cells from patients with and without endometriosis independently of the progesterone receptor pathway. Researchers isolated cells from surgical specimens and treated them with various agents, finding that cAMP and forskolin significantly increased prolactin secretion, a marker of decidualization, whereas progestins alone were ineffective. The induction effect was further enhanced by combining cAMP or forskolin with medroxyprogesterone acetate but not with progesterone, and this process occurred regardless of the intensity of progesterone receptor staining in the tissue. This paper is centrally about endometriosis — specifically exploring alternative signaling pathways for inducing decidualization as a potential therapeutic strategy for the condition.

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Abstract

Can decidualization be induced in endometrial stromal cells of endometriosis patients independent from the progesterone receptor pathway?
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Methods

Endometrium of patients with and without endometriosis was obtained from surgical treatments at the University Hospital of Duesseldorf. Endometrial progesterone receptor status was determined by immunohistochemistry and analyzed semi-quantitatively. Endometrial stromal cells (ESCs) were isolated from all endometria by combined enzymatic and mechanical treatment. Stromal cells were cultured in 6-well plates and treated at confluence with progesterone (0.1 – 1µM), MPA (1µM), cAMP (0.5 mM) and forskolin (25µM) alone or with progestins in combination with cAMP or forskolin for 6 days. The induction of decidualization was determined by quantification of secreted prolactin by ELISA (IBL). In parallel, cell number per 6-well was evaluated.

Results

In ESCs of all patients with and without endometriosis, decidualization was not induced by progestin treatment alone after 6-days, but the prolactin secretion significantly increased by cAMP as well as forskolin treatment. This effect of cAMP/forskolin on decidualization induction was enhanced by a combined treatment with MPA, but not with progesterone in endometrial stromal cells of patients with as well as without endometriosis. In general, cell number significantly decreased after successful induction of decidualization. No correlation of the effect of the different treatments to the intensity of progesterone receptor staining in the eutopic endometrial tissue could be observed.

Conclusion

The decidualization of ESCs from patients with endometriosis can be successfully induced by activation of the cAMP signaling pathway. This effect can be increased by a combined treatment with MPA. This represents a promising approach for the development of a new therapeutic tool for the treatment of endometriosis.

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endometriosis

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