LXR pathway drives hormonal response intensity in polycystic ovary syndrome.

IF 9 1区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

EMBO Molecular Medicine Pub Date : 2025-05-21 DOI:10.1038/s44321-025-00251-1

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

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引用次数: 0

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.

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LXR通路驱动多囊卵巢综合征激素反应强度。

在辅助生殖技术（ART）过程中，用于刺激卵母细胞生成的促性腺激素注射与易感多囊卵巢综合征（PCOS）患者异常反应的风险相关。肝X受体（Liver X receptors， LXR）通路在这一过程中被确定为关键的调节因子。本研究探讨激素信号、细胞网络和甾醇信号与炎症和免疫浸润的分子机制的整合。在野生型环境下，LXR的药理激活可以防止促性腺激素过度刺激，这与在LXR缺陷小鼠中观察到的效果一致。卵巢刺激导致免疫细胞浸润由颗粒细胞在缺乏LXR的情况下，导致颗粒细胞对促性腺激素的反应改变和炎症增强。LXR通过调节壁粒细胞中硫氧还蛋白相互作用蛋白（TXNIP）基因表达来控制炎性体活性，从而调节il - 1β的产生。这种免疫细胞浸润在PCOS患者的整个排卵过程中持续存在，并在卵丘细胞复合体中观察到，突出了LXR通路在抗逆转录病毒治疗过程中激素刺激过程中调节炎症过程的关键作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

EMBO Molecular Medicine 医学-医学：研究与实验

CiteScore

17.70

自引率

0.90%

发文量

105

审稿时长

4-8 weeks

期刊介绍： EMBO Molecular Medicine is an open access journal in the field of experimental medicine, dedicated to science at the interface between clinical research and basic life sciences. In addition to human data, we welcome original studies performed in cells and/or animals provided they demonstrate human disease relevance. To enhance and better specify our commitment to precision medicine, we have expanded the scope of EMM and call for contributions in the following fields: Environmental health and medicine, in particular studies in the field of environmental medicine in its functional and mechanistic aspects (exposome studies, toxicology, biomarkers, modeling, and intervention). Clinical studies and case reports - Human clinical studies providing decisive clues how to control a given disease (epidemiological, pathophysiological, therapeutic, and vaccine studies). Case reports supporting hypothesis-driven research on the disease. Biomedical technologies - Studies that present innovative materials, tools, devices, and technologies with direct translational potential and applicability (imaging technologies, drug delivery systems, tissue engineering, and AI)