LXR pathway drives hormonal response intensity in polycystic ovary syndrome
Abstract Gonadotropin injections used to stimulate oocyte production during assisted reproductive technology (ART) procedures are associated with the risk of an abnormal response in predisposed patients suffering polycystic ovary syndrome (PCOS). Liver X receptors (LXR) pathway has been identified a...
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| Format: | Article |
| Language: | English |
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Springer Nature
2025-05-01
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| Series: | EMBO Molecular Medicine |
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| Online Access: | https://doi.org/10.1038/s44321-025-00251-1 |
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| author | Sarah Dallel Manon Despalles Margaux Tore Yoan Renaud Ayhan Kocer Christelle Damon-Soubeyrand Pierre Pouchin Caroline Vachias Katia Boutourlinsky Céline Gonthier-Gueret Angélique De Haze Phelipe Sanchez Jean-Christophe Pointud Erwan Bouchareb Marine Vialat Aurélie Lagarde Cristina Gulunga Laure Chaput Aurélie Vega Florence Brugnon Igor Tauveron Amalia Trousson Cyrille de Joussineau Françoise Degoul Laurent Morel Jean Marc Lobaccaro Salwan Maqdasy Silvère Baron |
| author_facet | Sarah Dallel Manon Despalles Margaux Tore Yoan Renaud Ayhan Kocer Christelle Damon-Soubeyrand Pierre Pouchin Caroline Vachias Katia Boutourlinsky Céline Gonthier-Gueret Angélique De Haze Phelipe Sanchez Jean-Christophe Pointud Erwan Bouchareb Marine Vialat Aurélie Lagarde Cristina Gulunga Laure Chaput Aurélie Vega Florence Brugnon Igor Tauveron Amalia Trousson Cyrille de Joussineau Françoise Degoul Laurent Morel Jean Marc Lobaccaro Salwan Maqdasy Silvère Baron |
| author_sort | Sarah Dallel |
| collection | DOAJ |
| description | Abstract Gonadotropin injections used to stimulate oocyte production during assisted reproductive technology (ART) procedures are associated with the risk of an abnormal response in predisposed patients suffering polycystic ovary syndrome (PCOS). Liver X receptors (LXR) pathway has been identified as key regulators during this process. This study explores the integration of the hormonal signals, cellular networks and molecular mechanisms linking sterol signaling with inflammation and immune infiltration. Pharmacological activation of LXR in a wild-type context protects against gonadotropin hyperstimulation mirroring the effect observed in LXR-deficient mice. Ovarian stimulation leads to immune cell infiltration orchestrated by granulosa cells in absence of LXR, resulting in an altered granulosa cell response to gonadotropin and enhanced inflammation. LXR controls inflammasome activity by regulating Thioredoxin Interacting Protein (TXNIP) gene expression in mural granulosa cells, thereby modulating IL1β production. This immune cell infiltration persists throughout ovulation in PCOS patients and is observed in cumulus oocytes complexes, highlighting the pivotal role of LXR path in regulating inflammatory processes during hormonal stimulation in ART procedures. |
| format | Article |
| id | doaj-art-c91c46cf60de48f184a90160fceb7a8a |
| institution | Kabale University |
| issn | 1757-4684 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | EMBO Molecular Medicine |
| spelling | doaj-art-c91c46cf60de48f184a90160fceb7a8a2025-08-20T03:46:25ZengSpringer NatureEMBO Molecular Medicine1757-46842025-05-011771666168510.1038/s44321-025-00251-1LXR pathway drives hormonal response intensity in polycystic ovary syndromeSarah Dallel0Manon Despalles1Margaux Tore2Yoan Renaud3Ayhan Kocer4Christelle Damon-Soubeyrand5Pierre Pouchin6Caroline Vachias7Katia Boutourlinsky8Céline Gonthier-Gueret9Angélique De Haze10Phelipe Sanchez11Jean-Christophe Pointud12Erwan Bouchareb13Marine Vialat14Aurélie Lagarde15Cristina Gulunga16Laure Chaput17Aurélie Vega18Florence Brugnon19Igor Tauveron20Amalia Trousson21Cyrille de Joussineau22Françoise Degoul23Laurent Morel24Jean Marc Lobaccaro25Salwan Maqdasy26Silvère Baron27Université Clermont Auvergne, iGReD, CNRS UMR 6293, INSERM U1103Université Clermont Auvergne, iGReD, CNRS UMR 6293, INSERM U1103Université Clermont Auvergne, iGReD, CNRS UMR 6293, INSERM U1103Université Clermont Auvergne, iGReD, CNRS UMR 6293, INSERM U1103Université Clermont Auvergne, iGReD, CNRS UMR 6293, INSERM U1103Université Clermont Auvergne, iGReD, CNRS UMR 6293, INSERM U1103Université Clermont Auvergne, iGReD, CNRS UMR 6293, INSERM U1103Université Clermont Auvergne, iGReD, CNRS UMR 6293, INSERM U1103Université Clermont Auvergne, iGReD, CNRS UMR 6293, INSERM U1103Université Clermont Auvergne, iGReD, CNRS UMR 6293, INSERM U1103Université Clermont Auvergne, iGReD, CNRS UMR 6293, INSERM U1103Université Clermont Auvergne, iGReD, CNRS UMR 6293, INSERM U1103Université Clermont Auvergne, iGReD, CNRS UMR 6293, INSERM U1103Université Clermont Auvergne, iGReD, CNRS UMR 6293, INSERM U1103Université Clermont Auvergne, iGReD, CNRS UMR 6293, INSERM U1103Université Clermont Auvergne, iGReD, CNRS UMR 6293, INSERM U1103Assistance Médicale à la Procréation, CECOS, CHU Clermont-FerrandAssistance Médicale à la Procréation, CECOS, CHU Clermont-FerrandAssistance Médicale à la Procréation, CECOS, CHU Clermont-FerrandCentre de Recherche en Nutrition Humaine d’AuvergneService d’Endocrinologie, Diabétologie et Maladies Métaboliques, CHU Clermont Ferrand, Hôpital Gabriel MontpiedUniversité Clermont Auvergne, iGReD, CNRS UMR 6293, INSERM U1103Université Clermont Auvergne, iGReD, CNRS UMR 6293, INSERM U1103Université Clermont Auvergne, iGReD, CNRS UMR 6293, INSERM U1103Université Clermont Auvergne, iGReD, CNRS UMR 6293, INSERM U1103Université Clermont Auvergne, iGReD, CNRS UMR 6293, INSERM U1103Université Clermont Auvergne, iGReD, CNRS UMR 6293, INSERM U1103Université Clermont Auvergne, iGReD, CNRS UMR 6293, INSERM U1103Abstract Gonadotropin injections used to stimulate oocyte production during assisted reproductive technology (ART) procedures are associated with the risk of an abnormal response in predisposed patients suffering polycystic ovary syndrome (PCOS). Liver X receptors (LXR) pathway has been identified as key regulators during this process. This study explores the integration of the hormonal signals, cellular networks and molecular mechanisms linking sterol signaling with inflammation and immune infiltration. Pharmacological activation of LXR in a wild-type context protects against gonadotropin hyperstimulation mirroring the effect observed in LXR-deficient mice. Ovarian stimulation leads to immune cell infiltration orchestrated by granulosa cells in absence of LXR, resulting in an altered granulosa cell response to gonadotropin and enhanced inflammation. LXR controls inflammasome activity by regulating Thioredoxin Interacting Protein (TXNIP) gene expression in mural granulosa cells, thereby modulating IL1β production. This immune cell infiltration persists throughout ovulation in PCOS patients and is observed in cumulus oocytes complexes, highlighting the pivotal role of LXR path in regulating inflammatory processes during hormonal stimulation in ART procedures.https://doi.org/10.1038/s44321-025-00251-1Polycystic Ovary SyndromeGranulosa CellsLiver X ReceptorsHormonal StimulationInflammasome |
| spellingShingle | Sarah Dallel Manon Despalles Margaux Tore Yoan Renaud Ayhan Kocer Christelle Damon-Soubeyrand Pierre Pouchin Caroline Vachias Katia Boutourlinsky Céline Gonthier-Gueret Angélique De Haze Phelipe Sanchez Jean-Christophe Pointud Erwan Bouchareb Marine Vialat Aurélie Lagarde Cristina Gulunga Laure Chaput Aurélie Vega Florence Brugnon Igor Tauveron Amalia Trousson Cyrille de Joussineau Françoise Degoul Laurent Morel Jean Marc Lobaccaro Salwan Maqdasy Silvère Baron LXR pathway drives hormonal response intensity in polycystic ovary syndrome EMBO Molecular Medicine Polycystic Ovary Syndrome Granulosa Cells Liver X Receptors Hormonal Stimulation Inflammasome |
| title | LXR pathway drives hormonal response intensity in polycystic ovary syndrome |
| title_full | LXR pathway drives hormonal response intensity in polycystic ovary syndrome |
| title_fullStr | LXR pathway drives hormonal response intensity in polycystic ovary syndrome |
| title_full_unstemmed | LXR pathway drives hormonal response intensity in polycystic ovary syndrome |
| title_short | LXR pathway drives hormonal response intensity in polycystic ovary syndrome |
| title_sort | lxr pathway drives hormonal response intensity in polycystic ovary syndrome |
| topic | Polycystic Ovary Syndrome Granulosa Cells Liver X Receptors Hormonal Stimulation Inflammasome |
| url | https://doi.org/10.1038/s44321-025-00251-1 |
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