着床期ウシ子宮内膜におけるCCモチーフケモカインリガンド2によるプロスタグランジン合成と胚接着の制御

概要

C-C motif chemokine ligand 2 (CCL2), which regulates immune cells, has been reported to be expressed in the bovine endometrium during pregnancy. However, the details of how CCL2 is involved in the implantation mechanism of bovine embryos are still unclear. The purpose of this study is to analyze the expression pattern and functional properties of CCL2 in the bovine endometrium and embryos.

The qPCR analysis of the tissue showed that not only the amount of CCL2, but also CCL8 and CXCL10 were high at the implantation stage. The amount of CCL2 was significantly high in IFNa treated bovine endometrial stromal (BES) cells in vitro. In bovine endometrial epithelial (BEE) cells, however, the amount of CCL8 and CXCL10 were significantly high in the treatment group, but not for CCL2. The mRNA of each chemokine receptors (CCR1, CCR2 and CXCR3) was detected in the endometrial tissues and cells by RT-PCR. Cellular proliferation of BEE and BES significantly increased by the CCL2 treatment. The amount of prostaglandin (PG) E2 synthases, PGES1 and PGES2, and PGF2 alpha synthase, AKR1C4, were high at the implantation stage compared with luteal stage. The amount of PGES2 and AKR1B1 were significantly increased by CCL2 treatment does-dependently in BEE. In BES, on the other hand, the amount of PGES3, AKR1A1 and AKR1C4 were increased by CCL2 treatment. The qPCR analysis of the tissue showed that there were no differences in the amount of PGs transporter transcripts (MRP4 and PGT) between the luteal and implantation stages. The amount of MRP4 and PGT were significantly high in CCL2 treated bovine endometrial epithelial (BEE) and stromal (BES) cells in vitro. The mRNA of chemokine receptors (CCR1, CCR2 and CXCR3) were detected in the bovine trophoblastic cells derived from the blastocyst (BT) by RT-PCR. The amount of PCNA and IFNt were significantly high in the BT treated with CCL2 compared to the control. CCL2 significantly increased the attachment rate of BT vesicles to BEE in in vitro co-culture system. The amount of OPN increased in BEE, and ICAM-1 increased both in BEE and BT by CCL2 treatment.

These results indicate that CCL2, which expression increased in bovine endometrium during implantation by embryonic factors, has the potential to regulate the synthesis and circulation of PGs in the endometrium and the embryo growth. In addition, CCL2 has a possibility of regulating the process of bovine embryo attachment to the endometrium by modulation of binding molecules.