早期妊娠过程中，滋养层细胞对母体组织的正常侵润涉及复杂的分子对话和调控，是决定正常胎盘形成以及正常妊娠的一个关键因素。滋养层细胞的侵润机制与肿瘤细胞的转移有诸多相似性，但与肿瘤细胞截然不同的是，滋养层细胞对于子宫的侵润受到来自母体和自身的多种旁分泌/自分泌因子的严格调控。
CXCL14是一种与免疫细胞趋化、肿瘤迁移密切相关的趋化因子。近日，中科院动物研究所段恩奎研究员带领的研究小组通过基因芯片筛选以及多种实验手段证明，在小鼠和人类妊娠中，CXCL14在早期母胎界面呈现高表达，并特异地定位于滋养层细胞。进一步的功能研究发现CXCL14能够有效地抑制滋养层细胞的侵润，这一作用是通过调节滋养层MMP-9和MMP-2的分泌量和活性来实现的。另外，因为CXCL14的特异性受体目前尚未发现，文章作者通过用生物素标记的CXCL14在母胎界面进行特异结合实验，发现CXCL14特异地结合于滋养层细胞，而不结合于蜕膜细胞，这提示滋养层细胞是CXCL14在母胎界面的靶细胞，并表达CXCL14的受体。以上结果揭示了CXCL14是早期妊娠中母胎界面负调控滋养层侵润的一个重要因子。
相关研究结果分别发表于Journal of cellular physiology(2009 Nov;221(2):448-57.) 和Endocrinology (2009 Oct 15. Epub ahead of print)。 这项工作得到了中科院动物研究所知识创新工程项目和“973"项目的资助。（生物谷Bioon.com）
生物谷推荐原始出处：
Journal of Cellular Physiology 22 Jul 2009
CXCL14 inhibits trophoblast outgrowth via a paracrine/autocrine manner during early pregnancy in mice
Haibin Kuang 1 2 3, Qi Chen 1 2, Xiujun Fan 1 2, Ying Zhang 1 2, Li Zhang 1 2, Hongying Peng 1, Yujing Cao 1, Enkui Duan 1 *
1State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, P.R. China
2Graduate School of the Chinese Academy of Sciences, Beijing, P.R. China
3Department of Physiology, School of Medicine, Nanchang University, Nanchang, P.R. China
CXCL14, a member of chemokine family, was previously known to participate in many pathophysiological events, such as leukocytes recruitment and tumor suppression. However, it remained largely unknown whether CXCL14 is a physiological player during early pregnancy. In this regard, our recent global gene microarray analysis has observed an implantation-specific expression profile of CXCL14 mRNA during early pregnancy in mice, showing its higher levels at implantation sites compared to inter-implantation sites, implicating a potential role of CXCL14 in the periimplantation events. In the present investigation, using Northern blot, in situ hybridization and immunostaining, we further demonstrated that uterine CXCL14 expression was specifically induced at embryo implantation site and expanded with subsequent decidualization process in a spatiotemporal manner. The implanting embryo also showed a highlighted expression of CXCL14 in the blastocyst trophectoderm and its derived ectoplacental cones (EPCs) during postimplantation development. In vitro functional study revealed that CXCL14 could significantly inhibit both primary and secondary trophoblast attachment and outgrowth, correlated with a stage-dependant downregulation of MMP-2 and/or MMP-9 activity. Moreover, it was found that biotinylated CXCL14 could specifically bind to trophoblast cells in vitro and in vivo, suggesting trophoblast cell, perhaps expressing the unidentified CXCL14 receptor, is a bioactive target of CXCL14. Collectively, our findings provide evidences supporting the contention that CXCL14 is an important paracrine/autocrine modulator regulating trophoblast outgrowth at the maternal-fetal interface during the process of pregnancy establishment. This study is clinically related since CXCL14 is also highly expressed in human receptive endometrium and trophoblasts.
