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. 2017 Oct 16:8:268.
doi: 10.3389/fendo.2017.00268. eCollection 2017.

The Roles of Anandamide, Fatty Acid Amide Hydrolase, and Leukemia Inhibitory Factor on the Endometrium during the Implantation Window

Na Cui  1 , Changyan Wang  2 , Zhiming Zhao  1 , Jie Zhang  1 , Yueming Xu  1 , Yang Yang  1 , Guimin Hao  1
Affiliations

The Roles of Anandamide, Fatty Acid Amide Hydrolase, and Leukemia Inhibitory Factor on the Endometrium during the Implantation Window

Na Cui et al. Front Endocrinol (Lausanne). .

Abstract

Background/aims: 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.

Conclusion: 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.

Keywords: anandamide; endocannabinoid system; endometrial receptivity; fatty acid amide hydrolase; leukemia inhibitory factor; unexplained infertility.

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Figures

Figure 1
Figure 1
The expressions of the endocannabinoid system and leukemia inhibitory factor (LIF) of the two groups. (A) The HE staining of the endometrium tissue of the patients in the two groups. (B,C) The levels of CB1 (B), fatty acid amide hydrolase (FAAH) (C), and LIF (D) of the patients in the unexplained infertility (UI) and control groups were measured by immunohistochemical staining. (E) The integral optical density (IOD) values of CB1, FAAH, and LIF of UI group (n = 28) and control group (n = 32). The expressions of FAAH and LIF of UI group were significantly lower than the control group. The experiments were repeated three times. The results were presented as mean. The significance of the variation was summarized in Table 5. *P < 0.05.
Figure 2
Figure 2
The production of leukemia inhibitory factor (LIF) by RL95-2 after the stimulation with anandamide (AEA) and cannoibind receptor agonists. (A) The morphology of RL95-2 in the culture. (B) RL95-2 was stimulated by different concentrations of AEA (1, 5, and 10 µmol/L) for 24–72 h. (C) The production of LIF by RL95-2 was increased when cultured with low dose of AEA (1–5 µmol/L), whereas high dose of AEA (50 µmol/L) inhibited the LIF production. The experiments were repeated three times. The results were presented as mean. The significance of the variation was summarized in Table 5. *P < 0.05.
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