CXCL14 inhibits trophoblast outgrowth via a paracrine/autocrine manner during early pregnancy in mice.

Full Abstract

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.

Author information

Author/s: Kuang, Haibin (H); Chen, Qi (Q); Fan, Xiujun (X); Zhang, Ying (Y); Zhang, Li (L); Peng, Hongying (H); Cao, Yujing (Y); Duan, Enkui (E);

Affiliation: State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, PR China.

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: Journal of cellular physiology (J Cell Physiol), published in United States. (Language: eng)

Reference: 2009-Nov; vol 221 (issue 2) : pp 448-57

Dates: Created 2009/08/27; Completed 2009/09/09;

PMID: 19626669, status: MEDLINE (last retrieval date: 9/9/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Animals
Autocrine Communication
Biotinylation
Cell Proliferation
Cells, Cultured
Chemokines, CXC - genetics; metabolism
Decidua - cytology; enzymology
Down-Regulation
Embryo Implantation
Embryo, Mammalian - cytology; enzymology

Female
Gene Expression Regulation, Developmental
Matrix Metalloproteinase 2 - metabolism
Matrix Metalloproteinase 9 - metabolism
Mice
Organ Specificity
Paracrine Communication
Pregnancy
Protein Transport
Trophoblasts - cytology; enzymology; metabolism

Associated Chemicals: CXCL14 protein, mouse (0) ; Chemokines, CXC (0) ; Matrix Metalloproteinase 2 (EC 3.4.24.24) ; Matrix Metalloproteinase 9 (EC 3.4.24.35)

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