Characterization of C-C motif chemokine ligand 4 in the porcine endometrium during the presence of the maternal-fetal interface

Chemokines and their receptors play a crucial role in embryo implantation at the maternal-fetal interface during pregnancy. In this study, we investigated the role of CCL4 in development of the porcine endometrium in the early gestational period. Porcine CCL4 showed high similarity with the human counterpart, and mRNA expression of CCL4 and its receptor (CCR5) was predominantly present in the endometrium during early pregnancy. Treatment with CCL4 increased proliferation of porcine uterine luminal epithelial (pLE) cells by activation of PI3K and MAPK signal transduction. In addition, CCL4 recovered the endoplasmic-reticulum stress-reduced proliferation and decreased the unfolded protein response in pLE cells. Besides, the lipopolysaccharide-activated NF-κB pathway was suppressed in response to CCL4 in pLE cells. Inhibition of CCR5 decreased the proliferation of pLE cells and activation of the PI3K and MAPK pathways by CCL4. Furthermore, CCL4 enhanced conceptus-maternal interactions between porcine trophectoderm (pTr) cells and pLE cells during early pregnancy by activating expression of migration and implantation-related genes. Collectively, the results suggest that CCL4 may improve successful implantation in early pregnancy in pigs.