Role of chemerin/CMKLR1 in the maintenance of early pregnancy

Abstract

Chemerin is a cytokine that attracts much attention in the reproductive process. This study aimed to explore the effects of chemerin and its receptor chemokine-like receptor 1 (CMKLR1) on the maintenance of early pregnancy. The expression levels of chemerin and CMKLR1 in the decidua tissues of 20 early normal pregnant women and 20 early spontaneous abortion women were examined byWestern blot and real-time polymerase chain reaction analyses. CMKLR1 receptor antagonist (α-NETA) was then intrauterinely injected into normal pregnant mice model to assess its effect on the outcome of pregnancy and the phosphorylation rate of ERK1/2 in decidua tissues.We found that the expression level of chemerin in women who had experienced early spontaneous abortion was lower than in those who had experienced normal early pregnancy (P < 0.01); conversely, CMKLR1 expression was higher in the former than in the latter (P < 0.01). In a pregnant-mouse model, the embryo resorption rate of α-NETA group was higher than that in the negative control group (61.5% vs. 10.8%) (P < 0.001). Compared with the control group, ERK1/2 phosphorylation in decidua tissues decreased in the α-NETA-treated group (P < 0.01). These results suggested that the inhibition of the chemerin/CMKLR1 signaling pathway can lead to the abortion of mouse embryos, and that chemerin/CMKLR1 may play an important role in the maintenance of early pregnancy possibly by regulating ERK1/2 phosphorylation.

The Role of the Adipokines in the Most Common Gestational Complications

“…To analyze the regulatory activity of chemerin in the maintenance of early pregnancy, Yang et al assessed the expression of chemerin and its receptors in the decidua tissues from women with spontaneous and planned selective abortions. They discovered the significantly increased chemerin expression and downregulated expression of its receptors (chemokine-like receptor-1 (CMKLR1)) in patients with spontaneous abortions [205]. The intrauterine injection of chemerin receptors' antagonist resulted in a higher rate of embryo resorption in mice and lower ERK1/2 phosphorylation rate in uterine tissue [205].…”

“…They discovered the significantly increased chemerin expression and downregulated expression of its receptors (chemokine-like receptor-1 (CMKLR1)) in patients with spontaneous abortions [205]. The intrauterine injection of chemerin receptors' antagonist resulted in a higher rate of embryo resorption in mice and lower ERK1/2 phosphorylation rate in uterine tissue [205]. Interestingly, they also described the association between the pre-pregnancy serum chemerin levels and the risk of spontaneous abortion in women with polycystic ovary syndrome (PCOS).…”

Novel CMKLR1 Inhibitors for Application in Demyelinating Disease

“…Furthermore, the calculated single dose LD 50 for α-NETA was 873 mg/kg, which by comparison is safer than caffeine (LD 50 367 mg/kg) 34 . A recent study reported that direct α-NETA injection (5 μg) into the uterine horn on days 6, 9 and 12 following fertilization resulted in significant embryo resorption, thus potentially contraindicating α-NETA for treatment during pregnancy 35 .…”

The In Vitro Effect of Prostaglandin E2 and F2α on the Chemerin System in the Porcine Endometrium during Gestation

“…A growing body of evidence suggests that chemerin may be responsible for the control of reproductive functions. It has been indicated that the inhibition of the chemerin signaling via the CMKLR1 receptor in the mice decidua results in embryo abortion [ 12 ]. Furthermore, it has been observed that in women who had early spontaneous abortions, the concentrations of chemerin in the blood plasma were decreased, whereas the expression of CMKLR1 in the decidua was found to be elevated [ 12 ].…”

“…It has been indicated that the inhibition of the chemerin signaling via the CMKLR1 receptor in the mice decidua results in embryo abortion [ 12 ]. Furthermore, it has been observed that in women who had early spontaneous abortions, the concentrations of chemerin in the blood plasma were decreased, whereas the expression of CMKLR1 in the decidua was found to be elevated [ 12 ]. The expression of the chemerin system (a collective term for chemerin and its receptors) was confirmed in brain structures responsible for reproductive functions, as well as in the lower branches of the hypothalamic-pituitary-ovarian axis and the female reproductive tract.…”