LXR pathway drives hormonal response intensity in polycystic ovary syndrome

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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Main Authors: 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
Format: Article
Language:English
Published: Springer Nature 2025-05-01
Series:EMBO Molecular Medicine
Subjects:
Polycystic Ovary Syndrome
Granulosa Cells
Liver X Receptors
Hormonal Stimulation
Inflammasome
Online Access:https://doi.org/10.1038/s44321-025-00251-1
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Summary: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.
ISSN:1757-4684

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