Investigation of changes in endocannabinoids and N-acylethanolamides in biofluids, and their correlations with female infertility
Investigation of changes in endocannabinoids and N-acylethanolamides in biofluids, and their correlations with female infertility
复制标题
生物体液中内源性大麻素和N-酰基乙醇酰胺的变化及其与女性不孕症的相关性研究
DOI：
10.1016/j.chroma.2017.06.029
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发表时间：
2017-08-04
影响因子：
4.1
通讯作者：
Guo, Ming-Quan
中科院分区：
文献类型：
--
作者：
Ding, Jun;Luo, Xiao-Tong;Guo, Ming-Quan
女性不孕症是一个世界性的医学问题，不孕症生物标志物的缺乏阻碍了及时采取预防和治疗措施的能力。有趣的是，在不孕女性的生物流体中观察到内源性大麻素（eCB）和N-酰基乙醇酰胺（NAE）的变化。因此，一些研究人员提出了使用生物流体中的eCB和NAE作为不育生物标志物的假设;然而，几乎没有证据来验证该假设。为了研究它们与女性不孕症的相关性，我们开发了一种磁性液体微萃取-化学衍生化（MLME-CD）方法，结合液相色谱-串联质谱法定量生物流体中的eCB和NAE。目标化合物先用磁性甲苯吸附纯化，再用4-（N，N-二甲氨基）苯甲酰氯（4-DMABC）标记。MLME-CD方法提供了几个优点，包括通过防止eCB的异构化获得可靠的定量结果，通过需要20分钟的样品制备获得高通量，以及检测限为3.0-54.3 fmol的良好灵敏度。日内、日间相对标准偏差均小于14.5%，加标回收率为87.4%~ 117.9%。然后对49名不孕妇女和53名生育妇女（对照）的血清以及21名不孕妇女和20名对照的卵巢卵泡液中的eCB和NAE浓度进行了定量。非配对t检验显示不孕妇女血清AEA、PEA及卵泡液OEA与健康对照组比较差异有显著性，曲线下面积在0.605 ~ 0.707之间。(C)2017作者由爱思唯尔公司出版
Female infertility is a worldwide medical problem, and the scarcity of infertility biomarkers has hindered the ability to launch preventive and therapeutic measures in a timely manner. Intriguingly, alterations in endocannabinoids (eCBs) and N-acylethanolamides (NAEs) have been observed in the biofluids of infertile females. Therefore, a hypothesis of using eCB and NAEs in biofluids as infertility biomarkers was proposed by several researchers; however, little evidence exists to verify the hypothesis. To investigate their correlations with female infertility, we developed a magnetic liquid microextraction-chemical derivatization (MLME-CD) method coupled with liquid chromatography-tandem mass spectrometry for the quantification of eCBs and NAEs in biofluids. The target compounds were first purified with magnetic toluene as sorbents, and then labeled with 4-(N,N-dimethyamino)benzoyl chloride (4-DMABC). The MLME-CD method offered several advantages, including reliable quantification results by preventing the isomerizadon of eCB, high throughput by requiring 20 min for sample preparation, and good sensitivity with limits of detection at 3.0-54.3 fmol. The intra-day and inter-day relative standard deviations were below 14.5%, and the recoveries were 87.4%-117.9%. Concentrations of eCBs and NAEs in the serum of 49 infertile women and 53 fertile women (controls), and in the ovarian follicular fluid of 21 infertile women and 20 controls were then quantified. Using unpaired t test analysis indicated significant differences in AEA and PEA in serum, and OEA in follicular fluid between infertile women and healthy controls, and the areas under the curve were in the range of 0.605-0.707. (C) 2017 The Authors. Published by Elsevier B.V.