cAMP-Response Element-Binding 3-Like Protein 1 (CREB3L1) is Required for Decidualization and its Expression is Decreased in Women with Endometriosis

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This study demonstrates that CREB3L1 is required for decidualization and shows its expression is decreased in the endometrium of women with endometriosis, linking it to progesterone-dependent pathogenesis.

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This study investigated the role of CREB3L1 in decidualization and its expression patterns in relation to progesterone signaling. The researchers validated that CREB3L1 is a progesterone receptor target gene in mice and found significantly decreased CREB3L1 expression in the endometrium of women with endometriosis compared to healthy controls. Functional assays using human endometrial stromal cells demonstrated that silencing CREB3L1 impaired decidualization by reducing ERK1/2 phosphorylation, indicating its necessity for this process. This paper is centrally about endometriosis — specifically linking reduced CREB3L1 expression and impaired decidualization to the pathogenesis of the disease via progesterone resistance.

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Abstract

Endometriosis is a major cause of infertility and pelvic pain, affecting more than 10% of reproductive-aged women. Progesterone resistance has been observed in the endometrium of women with this disease, as evidenced by alterations in progesterone-responsive gene and protein expression. cAMP-Response Element-Binding 3-like protein 1 (Creb3l1) has previously been identified as a progesterone receptor (PR) target gene in mouse uterus via high density DNA microarray analysis. However, CREB3L1 function has not been studied in the context of endometriosis and uterine biology. In this study, we validated progesterone (P4) regulation of Creb3l1 in the uteri of wild-type and progesterone receptor knockout (PRKO) mice. Furthermore, we observed that CREB3L1 expression was significantly higher in secretory phase human endometrium compared to proliferative phase and that CREB3L1 expression was significantly decreased in the endometrium of women with endometriosis. Lastly, by transfecting CREB3L1 siRNA into cultured human endometrial stromal cells (hESCs) prior to hormonal induction of in vitro decidualization, we showed that CREB3L1 is required for the decidualization process. Interestingly, phosphorylation of ERK1/2, critical factor for decidualization, was also significantly reduced in CREB3L1-silenced hESCs. It is known that hESCs from patients with endometriosis show impaired decidualization and that dysregulation of the P4-PR signaling axis is linked to a variety of endometrial diseases including infertility and endometriosis. Therefore, these results suggest that CREB3L1 is required for decidualization in mice and humans and may be linked to the pathogenesis of endometriosis in a P4-dependent manner.
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cAMP-Response Element-Binding 3-Like Protein 1 (CREB3L1) is Required for Decidualization and its Expression is Decreased in Women with Endometriosis Public DepositedAdd to collection You do not have access to any existing collections. You may create a new collection. Downloadable Content Download PDFCitation MLA Ahn, , et al. Camp-response Element-binding 3-like Protein 1 (creb3l1) Is Required for Decidualization and Its Expression Is Decreased In Women with Endometriosis. 2016. https://doi.org/10.17615/kmrx-tn02APA Ahn., Yoo., Kim., Ferguson., Fazleabas., Young., Lessey., Lim., & Jeong. (2016). cAMP-Response Element-Binding 3-Like Protein 1 (CREB3L1) is Required for Decidualization and its Expression is Decreased in Women with Endometriosis. https://doi.org/10.17615/kmrx-tn02Chicago Ahn, , Yoo Yoo, Kim Kim, Ferguson Ferguson, Fazleabas Fazleabas, Young Young, Lessey Lessey et al. 2016. Camp-Response Element-Binding 3-Like Protein 1 (creb3l1) Is Required for Decidualization and Its Expression Is Decreased In Women with Endometriosis. https://doi.org/10.17615/kmrx-tn02- Creator - Ahn, - Other Affiliation: Laboratory of Stem Cell and Bioevaluation; Major in Biomodulation; Seoul National University - Yoo, - Other Affiliation: Department of Obstetrics and Gynecology and Reproductive Biology; Michigan State University; College of Human Medicine - Kim, - Other Affiliation: Department of Obstetrics and Gynecology and Reproductive Biology; Michigan State University; College of Human Medicine - Kim, - Other Affiliation: Laboratory of Stem Cell and Bioevaluation; Major in Biomodulation; Seoul National University - Ferguson, - Other Affiliation: Department of Obstetrics and Gynecology and Reproductive Biology; Michigan State University; College of Human Medicine - Fazleabas, - Other Affiliation: Department of Women’s Health; Spectrum Health System - Young, - School of Medicine, Department of Obstetrics and Gynecology - Lessey, - Other Affiliation: Department of Obstetrics and Gynecology; University Medical Group; Greenville Hospital System - Ahn, - Other Affiliation: Department of Agricultural Biotechnology; Seoul National University - Lim, - Other Affiliation: Laboratory of Stem Cell and Bioevaluation; Major in Biomodulation; Seoul National University - Jeong, - Other Affiliation: Department of Women’s Health; Spectrum Health System - Ahn, - Abstract - Endometriosis is a major cause of infertility and pelvic pain, affecting more than 10% of reproductive-aged women. Progesterone resistance has been observed in the endometrium of women with this disease, as evidenced by alterations in progesterone-responsive gene and protein expression. cAMP-Response Element-Binding 3-like protein 1 (Creb3l1) has previously been identified as a progesterone receptor (PR) target gene in mouse uterus via high density DNA microarray analysis. However, CREB3L1 function has not been studied in the context of endometriosis and uterine biology. In this study, we validated progesterone (P4) regulation of Creb3l1 in the uteri of wild-type and progesterone receptor knockout (PRKO) mice. Furthermore, we observed that CREB3L1 expression was significantly higher in secretory phase human endometrium compared to proliferative phase and that CREB3L1 expression was significantly decreased in the endometrium of women with endometriosis. Lastly, by transfecting CREB3L1 siRNA into cultured human endometrial stromal cells (hESCs) prior to hormonal induction of in vitro decidualization, we showed that CREB3L1 is required for the decidualization process. Interestingly, phosphorylation of ERK1/2, critical factor for decidualization, was also significantly reduced in CREB3L1-silenced hESCs. It is known that hESCs from patients with endometriosis show impaired decidualization and that dysregulation of the P4-PR signaling axis is linked to a variety of endometrial diseases including infertility and endometriosis. Therefore, these results suggest that CREB3L1 is required for decidualization in mice and humans and may be linked to the pathogenesis of endometriosis in a P4-dependent manner. - Date of publication - 2016 - Keyword - DOI - Identifier - PMCID: PMC5356025 - Publisher DOI: https://doi.org/10.2174/1566524016666160225153659 - Onescience id: cf6646fb45c77b7bfd872619585a340b194d022b - Resource type - Article - Rights statement - In Copyright - Journal title - Current Molecular Medicine - Journal volume - 16 - Journal issue - 3 - Page start - 276 - Page end - 287 - Language - English - ISSN - 1566-5240 - 1875-5666 Relations - Parents: This work has no parents. Items | Thumbnail | Title | Date Uploaded | Visibility | Actions | |---|---|---|---|---| | PubMedCentral-PMC5356025.pdf | 2016 | Public | Download |

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