Hum. Reprod. Advance Access originally published online on August 17, 2007
Human Reproduction 2007 22(10):2733-2742; doi:10.1093/humrep/dem208
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Regulation of C-C motif chemokine ligand 2 and its receptor in human decidual stromal cells by pregnancy-associated hormones in early gestation
1 Laboratory for Reproductive Immunology, Hospital and Institute of Obstetrics and Gynecology, Fudan University Shanghai Medical College, Shanghai 200011, People's Republic of China 2 Department of Obstetrics and Gynecology, The Affiliated Hospital, Hainan Medical College, Haikou 570102, People's Republic of China
3 Correspondence address. Tel: (+0086)021-63457331; Fax: (+0086)021-63457331; E-mail: djli{at}shmu.edu.cn
BACKGROUND: Decidua is in close contact with the fetal trophoblasts, and involved in immune relationship of mother to fetus. However, the roles of decidua and decidual stromal cells (DSC) in materno-fetal immune regulation remain to be elucidated. In the present study, the expression and regulation of chemokines and their receptors in decidua and DSCs were investigated.
METHODS AND RESULTS: The transcription of 18 chemokine receptors in human first-trimester decidual tissue and DSC were first analysed by RT-PCR. Among these receptors, C-C motif chemokine receptor-2 (CCR2) was highly transcribed. It was demonstrated by RT-PCR and immunostaining that both CCR2 and its major ligand, C-C motif chemokine ligand 2 (CCL2, monocyte chemoattractant protein-1), were expressed in decidua and DSC. We then detected CCL2 in the supernatant of primary cultures of DSC by enzyme-linked immunosorbent assay. It was shown that DSC secreted CCL2 spontaneously and continuously over 72 h (21.72 ± 2.34 ng/ml), and the CCR2 antagonist RS102895 and an inhibitor of the map kinase kinase/mitogen-activated protein kinase (ERK/MAPK) signal pathway decreased significantly the CCL2 secretion of DSC (both P < 0.05). We further studied effects of the pregnancy-associated hormones, estrogen, progesterone or HCG on CCL2 secretion by DSC. CCL2 secretion by DSC was up-regulated by estrogen, progesterone or HCG.
CONCLUSIONS: CCR2 and CCL2 are co-expressed by human first-trimester DSC and decidual tissue. CCL2 is secreted in an autocrine manner through the ERK/MAPK pathway, and is up-regulated by the pregnancy-associated hormones, estrogen, progesterone and HCG, which suggests that CCL2 may play an important role at materno-fetal interface.
Key words: decidual stromal cells/C-C motif chemokine ligand 2/C-C motif chemokine receptor-2/materno-fetal interface/immune regulation
Submitted on September 4, 2006; resubmitted on June 6, 2007; accepted on June 14, 2007.
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