Scope: Luteal phase deficiency (LPD) is the main cause of infertility without an effective cure. Quercetin (QUE) is a bioactive flavonoid with antioxidant properties, while its role in treating LPD remains unclear. This study aims to investigate the therapeutic effects of QUE on infertility and menstrual disorders induced by LPD, thus further exploring the underlying mechanism.Methods and results: Mifepristone‐induced rats are used to explore the protective effects of QUE against LPD. QUE stimulates the spontaneous secretion of progesterone to improve luteal function and endometrial receptivity in LPD rats by activating the kisspeptin/GPR54 system to facilitate the gonadotropin‐releasing hormone (GnRH) pulsatility. Bioinformatics analysis reveals that the core mechanism of QUE in treating LPD is to attenuate the GnRH neuron pyroptosis by inhibiting the NF‐κB pathway, which is further verified in LPD rats and lipopolysaccharide (LPS)‐treated GT1‐7, as QUE significantly reduces the expression of key factors concerning NF‐κB pathway and NOD‐like receptor family pyrin domain‐containing 3 (NLRP3) inflammasome.Conclusion: This study first proposes that neuron pyroptosis‐induced GnRH pulsatility disruption accounts for the pathogenesis of LPD, and QUE facilitates the pulse secretion of GnRH to boost the spontaneous progesterone secretion by inhibiting NF‐κB/NLRP3‐mediated neuron pyroptosis, which provides a new therapeutic target and strategy for LPD.

中文翻译：

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槲皮素通过抑制 NF-κB/NLRP3 介导的神经元焦亡促进搏动性促性腺激素释放激素释放以改善黄体功能


范围： 黄体期缺陷 （LPD） 是没有有效治愈方法的不孕症的主要原因。槲皮素 （QUE） 是一种具有抗氧化特性的生物活性类黄酮，但其在治疗 LPD 中的作用尚不清楚。本研究旨在探讨 QUE 对 LPD 诱导的不孕症和月经紊乱的治疗效果，从而进一步探讨其潜在机制。方法和结果： 使用米非司酮诱导的大鼠来探索 QUE 对 LPD 的保护作用。QUE 通过激活 kisspeptin/GPR54 系统促进促性腺激素释放激素 （GnRH） 搏动，刺激黄体酮的自发分泌，改善 LPD 大鼠的黄体功能和子宫内膜容受性。生物信息学分析显示，QUE 治疗 LPD 的核心机制是通过抑制 NF-κB 通路来减弱 GnRH 神经元焦亡，这在 LPD 大鼠和脂多糖 （LPS） 处理的 GT1-7 中得到进一步验证，因为 QUE 显着降低与 NF-κB 通路和 NOD 样受体家族含热蛋白结构域 3 （NLRP3） 炎性小体有关的关键因子的表达。结论： 本研究首先提出神经元焦亡诱导的 GnRH 搏动破坏是 LPD 发病机制的原因，QUE 通过抑制 NF-κB/NLRP3 介导的神经元焦亡促进 GnRH 的脉冲分泌以促进自发性孕激素分泌，为 LPD 提供了新的治疗靶点和策略。