Inhibition of epidermal growth factor receptor restores decidualization markers in stromal fibroblasts from women with endometriosis

David W. Erikson, Joseph C. Chen, Terhi Piltonen, Marco Conti, Juan C. Irwin, Linda C. Giudice
In: Journal of Endometriosis and Pelvic Pain Disorders · 2014 · vol. 6(4) , pp. 196–211 · doi:10.5301/je.5000198 · W1964159088
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⚙ AI-generated summary by claude@2026-06, 2026-06-07 ⓘ

Inhibition of epidermal growth factor receptor signaling restored decidualization marker expression in endometrial stromal fibroblasts from women with endometriosis.

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⚙ AI-generated deep summary by claude@2026-06, 2026-06-07 ⓘ

This study investigated whether inhibiting PI3K/AKT/mTOR, MAPK, and EGFR signaling could restore cAMP-induced decidualization marker expression in human endometrial stromal fibroblasts from women with endometriosis compared with those without disease. Endometrial stromal fibroblasts were treated in vitro with 8-bromoadenosine 3’,5’-cyclic monophosphate to induce decidualization, with or without chemical inhibitors to EGFR (gefitinib), mTOR (rapamycin), or MEK1/2 (UO126), and decidualization was assessed by qPCR for IGFBP1, PRL, and FOXO1A. Gefitinib specifically restored expression of these decidualization markers in endometriosis-derived stromal fibroblasts to levels comparable to non-endometriosis cells and reduced phosphorylated mTOR during 8-br-cAMP treatment, with additional analyses suggesting dysregulated EGFR negative feedback regulators. A key limitation is the small sample size (n=5 per group) and that the work was performed in vitro on isolated cells rather than in vivo. This paper is centrally about endometriosis — it tests EGFR inhibition to correct aberrant cAMP-induced decidualization marker expression in stromal fibroblasts from women with the disease.

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Abstract

Purpose Decidualization comprises specific biochemical and morphological changes in uterine endometrium essential for establishment of pregnancy. This process is abnormal in women with endometriosis, a disorder in which endometrial-like tissue is present outside the uterus. The aim of this study was to restore cAMP-induced decidualization marker expression in endometrial stromal fibroblasts from women with endometriosis by using chemical inhibitors to PI3K/AKT/mammalian target of rapamycin (mTOR), mitogen-activated protein kinase (MAPK) and epidermal growth factor receptor (EGFR) signaling pathways in vitro. Methods Endometrial stromal fibroblasts (eSF) from women with (eSF endo ) and without (eSF non-endo ) endometriosis were treated with inhibitors to EGFR tyrosine kinase (gefitinib), mTOR (rapamycin) and MAPK kinase 1/2 (MEK1/2) (UO126) during 8-bromoadenosine 3′,5′-cyclic monophosphate (8-br-cAMP)–stimulated decidualization. Decidualization was assessed by evaluating expression of insulin growth factor binding protein 1 (IGFBP1), prolactin (PRL) and forkhead box protein O1A (FOXO1A) by quantitative real-time PCR. Results Gefitinib restored expression of decidualization markers in eSF endo to levels consistent with those in eSF non-endo . Elevated levels of phosphorylated mTOR in eSF endo were reduced to levels found in eSF non-endo , by gefitinib during treatment with 8-br-cAMP. Additional gene expression analyses suggested dysregulation of EGFR negative feedback regulators in eSF endo . Conclusions Results implicate EGFR signaling as an underlying cause for aberrant cAMP-induced decidualization in women with endometriosis, and provide a potential target for management of infertility associated with the disease. The reduction of p-mTOR levels in eSF endo during 8-br-cAMP treatment suggests cooperation between EGR and protein kinase A signaling in the regulation of mTOR in eSF.

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endometriosisinfertility

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