Mitigation of ER-stress and inflammation by chemokine (C-C motif) ligand 21 during early pregnancy

The immune system plays an important role in pregnancy. Chemokines recruit leukocytes at the maternal-fetal interface during early pregnancy. However, the role of the chemokine, C-C motif chemokine ligand 21 (CCL21), is less known. The aim of this study was to identify the expression of CCL21 and its receptor, CCR7, in the endometrium during estrous cycle and early pregnancy, and to investigate the functional effects of CCL21 on porcine trophectoderm (pTr) and porcine uterine luminal epithelial (pLE) cells. Our results indicated that CCL21 and CCR7 are increased in the glandular (GE) and luminal epithelium (LE) of the endometrium during early pregnancy, compared to estrous pigs. Recombinant CCL21 improved pTr and pLE cell proliferation through activation of the PI3K and MAPK pathways and suppression of tunicamycin-induced endoplasmic reticulum (ER) stress or LPS-induced inflammation. Collectively, these results provide novel insights into CCL21-mediated signaling mechanisms at the maternal-fetal interface during early pregnancy.