Zhang Qingqing, Xiao Zhonglin, Lee Cheuk-Lun, Duan Yong-Gang, Fan Xiujun, Yeung William S B, Chiu Philip C N, Zhang Jian V
Shenzhen Key Laboratory of Fertility Regulation, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China.
Department of Obstetrics and Gynecology, The University of Hong Kong, Hong Kong, Hong Kong SAR, China.
Front Cell Dev Biol. 2022 May 17;10:883636. doi: 10.3389/fcell.2022.883636. eCollection 2022.
Chemerin is an adipokine that regulates metabolism in pregnancy. An elevation of serum chemerin level is associated with pregnancy complications. Consistently, we demonstrated that the chemerin expression was increased in placenta of preeclamptic patients at deliveries. The G protein-coupled receptor chemokine-like receptor 1 (CMKLR1) mediates the actions of chemerin. The functions of the chemerin-CMKLR1 axis in maintaining pregnancy are still unknown. In this study, we demonstrated that CMKLR1 was expressed in the decidual natural killer (dNK) cells and chorionic villi of human. Chemerin suppressed the proliferation of the dNK cells . Specific antagonist of CMKLR1, α-Neta abolished the suppressive effect of spent medium from chemerin-treated dNK cells culture on extravillous trophoblast invasion. Activation of the chemerin-CMKLR1 axis promoted fusion and differentiation of human cytotrophoblast to syncytiotrophoblast . We generated knockout mice and showed that the deficiency negatively affected pregnancy outcome in terms of number of implantation sites, litter size and fetal weight at birth. Histologically, the deficiency impaired formation of the syncytiotrophoblast layer II, induced enlargement of the maternal lacunae in the labyrinth, increased the diameter of the spiral arteries and increased trophoblast invasion in the decidua. The deficient placenta also displayed an increased number of dNK cells and serum IL-15 level. In summary, the chemerin-CMKLR1 axis regulated placental development and spiral artery remodeling in early pregnancy.
Chemerin是一种调节孕期新陈代谢的脂肪因子。血清Chemerin水平升高与妊娠并发症有关。同样，我们证明在子痫前期患者分娩时胎盘组织中Chemerin表达增加。G蛋白偶联受体趋化因子样受体1（CMKLR1）介导Chemerin的作用。Chemerin-CMKLR1轴在维持妊娠中的功能尚不清楚。在本研究中，我们证明CMKLR1在人蜕膜自然杀伤（dNK）细胞和绒毛膜绒毛中表达。Chemerin抑制dNK细胞的增殖。CMKLR1的特异性拮抗剂α-Neta消除了经Chemerin处理的dNK细胞培养上清对绒毛外滋养层细胞侵袭的抑制作用。激活Chemerin-CMKLR1轴促进人细胞滋养层细胞向合体滋养层细胞的融合和分化。我们构建了基因敲除小鼠，并发现该基因缺陷在着床位点数量、窝仔数和出生时胎儿体重方面对妊娠结局产生负面影响。组织学上，该基因缺陷损害了合体滋养层第二层的形成，导致迷路中母体腔隙扩大，螺旋动脉直径增加，并增加了滋养层细胞在蜕膜中的侵袭。该基因缺陷的胎盘还显示dNK细胞数量增加和血清IL-15水平升高。总之，Chemerin-CMKLR1轴在妊娠早期调节胎盘发育和螺旋动脉重塑。
