Follicular Fluid Soluble Receptor for Advanced Glycation End-Products (sRAGE): A Potential Indicator of Ovarian Reserve

Follicular Fluid Soluble Receptor for Advanced Glycation End-Products (sRAGE): A Potential Indicator of Ovarian Reserve
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DOI:
10.1210/jc.2013-3839
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发表时间:
2014-02-01
影响因子:
5.8
通讯作者:
Ambroggio, Jennifer
Ambroggio, Jennifer
中科院分区:
医学2区
文献类型:
--
作者:
Merhi, Zaher;Irani, Mohamad;Ambroggio, Jennifer

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背景:晚期糖基化终产物(AGEs)与其细胞受体(RAGE)的相互作用参与了卵泡异常生长的发病机制。RAGE具有一种循环的分泌受体形式,即可溶性RAGE(SRAGE),它中和AGEs的作用,可能对卵泡环境起保护作用。目的:研究血清或卵泡液(FF)sRAGE水平是否与卵巢储备标志物相关。设计、背景和参与者:31名育龄妇女的血清抗苗勒氏激素(AMH)和sRAGE蛋白水平相关。另有33名接受体外受精的妇女入选。主要观察指标:卵丘细胞AMH和AMHR-II基因表达、血清和血清AMH及SRAGE蛋白浓度。结果:血清中SAGE水平与体重指数(BMI)呈负相关(r=-0.5,P<0.01),与年龄及血清AMH无关。FFSRAGE越高,每个周期所需的促性腺激素国际单位数越低,与年龄、BMI或第3天FSH水平无关(r=-0.4,P=0.04)。在调整了年龄、BMI、第3天FSH和促性腺激素的总剂量后,FF Sage预测了取卵的数量(R2=0.27,P=0.045)。FFsage与FFAMH水平呈正相关(r=0.5,P=0.0085)。RT-PCR结果显示,FFSRAGE与AMH或AMHR-II的mRNA水平无相关性。结论:这些数据支持FFSRAGE与卵巢储备的测量之间的关系。有害炎症AGEs在卵泡健康中的病理意义尚需进一步研究。靶向AGEs可能为卵巢反应减弱的治疗提供潜在的治疗选择。
Context: The interaction of advanced glycation end-products (AGEs) with their cellular receptor (RAGE) is implicated in the pathogenesis of abnormal ovarian follicular growth. RAGE has a circulating secretory receptor form, soluble RAGE (sRAGE), which neutralizes the action of AGEs and might exert a protective role on the follicular environment.Objective: The objective of the study was to investigate whether serum or follicular fluid (FF) sRAGE levels are associated with markers of ovarian reserve.Design, Setting, and Participants: Serum anti-Mullerian hormone (AMH) and sRAGE protein levels were correlated in 31 reproductive-aged women. An additional 33 women who underwent oocyte retrieval for in vitro fertilization were enrolled. AMH and its receptor (AMHR-II) mRNA levels were quantified in cumulus granulosa cells and FF sRAGE and AMH protein levels were measured.Main Outcome Measures: Granulosa cell AMH and AMHR-II gene expression, serum and FF AMH and sRAGE protein concentration, and number of oocytes retrieved were measured.Results: In the serum, sRAGE levels were negatively correlated with body mass index (BMI) (r = -0.5, P < .001) but not with age or serum AMH. The higher the FF sRAGE, the lower the number of international units of gonadotropin needed per cycle independent of age, BMI, or day 3 FSH level (r =- 0.4, P = .04). After adjusting for age, BMI, day 3 FSH, and the total dose of gonadotropins, FF sRAGE predicted the number of oocytes retrieved (R-2 = 0.27, P = .045). FF sRAGE positively correlated with FF AMH levels (r = 0.5, P = .0085). RT-PCR results showed no correlation between the FF sRAGE and AMH or AMHR-II mRNA levels.Conclusion: These data support a relationship between FF sRAGE and measures of ovarian reserve. The pathological significance of the harmful inflammatory AGEs in follicular health clearly requires further investigation. Targeting AGEs might offer potential therapeutic options for the treatment of diminished ovarian response.