目的:我们研究了内源性大麻素系统(ECS)在不明原因不孕症(UI)患者子宫内膜中的作用,Anandamide(AEA)对白血病抑制因子(LIF)的影响。
方法:患者分为UI组和对照组。在黄体中期收集子宫内膜样品。1型大麻素(CB1)的水平,脂肪酸酰胺水解酶(FAAH),并检查了LIF。AEA后测量LIF产量,CB1拮抗剂AM251和CB2拮抗剂AM630刺激。
结果:可用胚胎率,成功植入和怀孕,UI组子宫内膜厚度明显低于对照组,提示UI组子宫容受性降低。FAAH和LIF水平显著下降,而UI组子宫内膜CB1轻度升高。通过低量的AEA给药(1-10μM)促进了LIF的产生,而较高浓度的AEA(50μM)降低了促进作用。与单独使用AEA相比,AM251或AM630降低了LIF水平。FAAH和LIF的表达与UI患者子宫容受性和种植率密切相关。不同浓度的AEA可以刺激LIF产生的动态变化。
结论:我们的数据表明ECS在人类生育中的重要作用,这可能会促进成功植入和治疗生殖疾病的新策略。
OBJECTIVE: We investigated the role of the endocannabinoid system (ECS) in the endometrium of unexplained infertility (UI) patients, and effect of
anandamide (AEA) on leukemia inhibitory factor (LIF).
METHODS: Patients were divided into UI and control groups. Endometrium samples were collected at the midluteal phase. Levels of cannabinoid type 1 (CB1), fatty acid amide hydrolase (FAAH), and LIF were examined. LIF productions were measured after AEA, CB1 antagonist AM251, and CB2 antagonist AM630 stimulation.
RESULTS: Rates of available embryo, successful implantation and pregnancy, and the endometrial thickness of UI group were significantly lower than control, suggesting uterine receptivity was decreased in UI group. FAAH and LIF levels were significantly decreased, whereas endometrial CB1 was slightly increased in UI group. LIF production was promoted by low amount of AEA administration (1-10 μM), while the promotion was reduced by higher concentration of AEA (50 μM). LIF levels were decreased by AM251 or AM630, compared with AEA alone. Expressions of FAAH and LIF were closely associated with uterus receptivity and implantation rate of UI patients. Different concentrations of AEA could stimulate dynamic changes in LIF production.
CONCLUSIONS: Our data indicated the important role of the ECS in human fertility, which may promote new strategies for successful implantation and treatments for reproductive diseases.