Secreted cyclophilin A induction during embryo implantation in a model of human trophoblast-endometrial epithelium interaction.
OBJECTIVE
Embryo implantation in the human is a complex process that is crucial for a successful pregnancy. Implantation involves complex interactions between the embryo and the maternal endometrium. In order to understand the critical events involved in human embryo implantation, we established a human trophoblast-endometrial interaction model to study the putative alterations of gene expression during implantation.


METHODS
Comparative proteomic analysis was applied to the co-culture and separated culture systems of the trophoblast cell line BeWo and human endometrial epithelial cell (EEC) line RL95-2. Comparing the secreted molecules resulted in an interesting finding that secreted cyclophilin A (CypA) was increased in the co-culture system. To further verify our observation, human recombinant CypA was applied to endometrial cells to understand the downstream gene regulation.


RESULTS
Cyclophilin A (CypA) was identified by MALDI-TOF Mass with higher expression levels in the co-cultured cells when compared to the endometrial cells alone. Western blot analysis further confirmed the increased expression of CypA in co-culture conditions. Immunoblotting analysis showed that both p38 MAPK and extracellular signal-regulated kinase (ERK) were activated in EEC.


CONCLUSIONS
Our results suggest that the secreted CypA plays a specific role in the signaling pathway of embryo implantation. The identification of CypA opens a new avenue for early embryo implantation research.
Department of Life Science, Tunghai University, Taichung, Taiwan, Republic of China.
Chih-Liang
CL
Tien
Chao-Hsiung
CH
Lin
Ting-Hui
TH
Lin
Feng-Chen
FC
Wen
Chien-Wei
CW
Su
Sheng-Seen
SS
Fan
Mingli
M
Hsieh
D045744:Cell Line, Tumor; D018920:Coculture Techniques; D021984:Cyclophilin A / Q000096:biosynthesis* / Q000378:metabolism / Q000494:pharmacology; D010064:Embryo Implantation / Q000502:physiology*; D004717:Endometrium / Q000502:physiology*; D004847:Epithelial Cells / Q000502:physiology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D006801:Humans; D008954:Models, Biological; D011247:Pregnancy; D040901:Proteomics; D014327:Trophoblasts / Q000502:physiology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D021984:Cyclophilin A