Abstract
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). 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. 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. 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.
Highlights
The unexplained infertility (UI) was proposed in 1960s, but efficient treatments are yet to be developed today [1]
The patients recruited to the study were women under the age of 38, with normal menstrual cycle and spontaneously ovulation, proposed to get in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) treatment in our center
A total of 28 patients were included in the UI group, who had no pregnancy after intrauterine insemination (IUI), excluding the uterine, endocrine, immune, and male factors
Summary
The unexplained infertility (UI) was proposed in 1960s, but efficient treatments are yet to be developed today [1]. The possible reasons could be that the ovum is not released at the optimum time for fertilization, the. Role of the ECS in Human Fertility sperm is difficult to access to the ovum, or the embryo fails to implant into the endometrium [3]. It is increasingly recognized that the embryonic implantation is of critical importance for successful fertilization [4]. The uterus exhibits maximal receptivity for random lying blastocyst in the implantation window phase. This period of receptivity is transient and results from the programmed sequence of the effect of sex hormones and cytokines on the endometrium. The disturbance of intrauterine environment might lead to the decreased uterine receptivity, which is one of the causes of the UI
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