PS-2 Early Intrauterine Suppression of CXCL12-CXCR4 Alters Expression of Placental Inflammatory Profile at Mid-to-Late Gestation

Abstract A proper balance of inflammatory cytokines at the fetal-maternal interface is crucial for successful embryo implantation and placental formation. Chemokine ligand 12 (CXCL12) receptor CXCR4 are expressed by fetal maternal tissues implicated in cytokine synthesis. However, mechanisms controlling axis profile not well characterized. Using an in-vivo sheep model, we previously demonstrated suppressing CXCL12-CXCR4 signaling during yielded dysregulated production placenta. Our objective was to determine if disrupting alters mid-to-late gestation. Day post-breeding, osmotic pumps were surgically installed 37 ewes deliver inhibitor (1.5X dose, n = 8; 1X 3X 8) or saline (n 13) into uterine lumen ipsilateral corpus luteum 14 days. On days 90 135 gestation, collected; (caruncle) (cotyledon) placenta components then separated analyzed. Real-time qPCR used measure gene expression pro-inflammatory tumor necrosis factor (TNF), interferon-γ (IFNγ), interleukin-12 (IL12), anti-inflammatory interleukin-10 (IL10) transforming growth factor-β (TGFβ). Gene TGFβ from pump on day increased (P < 0.03) caruncles 3x treated compared control while IL10 mRNA decreased 0.02) cotyledons 1.5x treatment. Furthermore, analysis 1x showed greater IL12 contralateral pump; meanwhile pump. High levels TGFβ, IFNγ (whose promoted IL12), TNF along with have been associated preeclampsia women. The changes expressions ovine immune a disrupted CXCL12-CCR4 may be related preeclamptic events. Ultimately, modulating CXCL12-induced actions novel approach manipulating environment when most pregnancy losses occur reveal methods improve reproductive success health livestock.