The chemokine receptor CXCR4 and its ligand CXCL12 are activated during implantation and placentation in sheep

Abstract

Abstract Background The progression of implantation and placentation in ruminants is complex and is regulated by interplay between sex steroids and local signaling molecules, many of which have immune function. Chemokines and their receptors are pivotal factors in implantation and vascularization of the placenta. Based on known critical roles for chemokine receptor 4 (CXCR4) during early pregnancy in other species, we hypothesized that CXCR4 and its ligand CXCL12 would increase in the endometrium and conceptus in response to implantation in ewes. The objectives of the current study were to determine if CXCL12 and CXCR4 were upregulated in: endometrium from pregnant compared to non-pregnant ewes and in, conceptuses, cotyledons, caruncles and intercaruncular tissue. Methods Tissues were collected from sheep on Days 12, 13, 14, and 15 of either the estrous cycle or pregnancy and from pregnant ewes on Days 35 and 50. Blood samples from jugular and uterine vein were also collected on all days. Conceptuses were collected from mature ewes on Days 13, 15, 16, 17, 21 and 30 of gestation. Real time PCR was used to determine relative mRNA concentrations for CXCL12 and CXCR4 and Western blot analysis was employed to confirm protein concentration. Results Differences described are P Conclusions A comprehensive analysis of CXCL12 and CXCR4 expression in fetal and maternal tissues during early pregnancy is reported with noteworthy differences occurring during implantation and placentation in sheep. We interpreted these data to mean that the CXCL12/CXCR4 pathway is activated during implantation and placentation in sheep and is likely playing a role in the communication between trophoblast cells and the maternal endometrium.

Keywords

• CXCR4
• CXCL12
• Placenta
• Trophoblast
• Implantation
• Sheep