Angiogenic DC‐SIGN+ cells are present at the attachment sites of epitheliochorial placentae

Abstract

Spontaneous early and mid-gestation fetal losses occur in swine. At both stages, endometrial lymphocytes associated with smaller, paler conceptuses have fewer pro-angiogenic and more pro-inflammatory cytokine transcripts compared with robust conceptuses. We hypothesized that similar differences occur in conceptus-associated dendritic cells (DCs). Using laser capture-microdissection, dendritic cell-specific intercellular adhesion molecule-grabbing non-integrin (DC-SIGN)(+) cells were isolated from attachment sites of healthy and arresting conceptuses at gestation day (gd)20 and 50. DC-SIGN(+) cells were screened using real-time PCR for vascular endothelial cell growth factor (Vegf), its receptors, semaphorins (Sema) and plexins (Plxn), and for toll-like receptor (Tlr) transcripts to address potential activation pathways. Homogenized endometrial and trophoblast biopsies were quantified for type 1/type 2 cytokine transcripts/proteins. DC-SIGN(+) cells from healthy and arresting conceptuses had more Vegf transcripts at early than mid gestation whereas transcripts for Vegfr1 and Vegfr2 were stable. In gd20 arresting site DC-SIGN(+) cells, Neuropilin-2 transcripts were elevated, whereas at gd50 arresting sites, Plxn-A2 increased and Sema3A transcripts were lost. Tlr-1, Tlr-4 and Tlr-6 transcript abundance was independent of conceptus health. At gd20, type 1 cytokines were prevalent, whereas at gd50 type 2 cytokines predominated in endometrium and trophoblast. Thus, gestational features, characteristic of haemochorial placentation, are present in species with distinctly different placentation.