PSI-2 Disruption of CXCL12-CXCR4 Axis at Fetal-Maternal Interface During Implantation Alters Ovine Angiogenic Expression at Mid-to-Late Gestation

Abstract Placental dysfunction originates during placental development, specifically the events of placentation. Vascularization is a key component placentation due to its role in fetal-maternal exchange. Cytokines are regulators development; signaling chemokine ligand 12 (CXCL12) and receptor (CXCR4) drives vascularization. Utilizing an vivo sheep model, we demonstrated that suppressing CXCL12-CXCR4 at interface reduces We hypothesized these negative impacts early gestation would result compromised development vascularization mid late gestation. On day post-breeding, osmotic pumps were surgically installed 37 ewes delivered either CXCR4 inhibitor (AMD3100) 1x dose (n = 8),1.5X 8), or 3X 8) saline 13) into uterine lumen ipsilateral corpus luteum for 14 days. 90 135 tissues collected maternal (caruncle) fetal (cotyledon) placenta components separated analyzed. Gene expression angiogenic factors analyzed using Real-time qPCR. was significantly altered by AMD3100 treatment vascular endothelial growth factor receptors (FLT-1 KDR) primarily contralateral luteum. Significant decreases KDR seen 3x compared control (P < 0.03), 1.5x 0.008), 0.01); however, FLT-1 increased 0.02) from 1.5x. Day caruncle tissue had significant increases (0.02), 0.03); decreased contralateral. Fibroblast 2 both cotyledon 0.03) 0.03). Our data underscore importance provide strong evidence altering CXCR4-mediated induces enduring effects later A greater understanding CXCL12/CXCR4 functions may reveal methods improve reproductive success health.