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 capturemicrodissection, 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.

The integrative roles of chemokines at the maternal–fetal interface in early pregnancy

“…It has long been accepted that T-cell activity at the fetal-maternal interface is skewed toward Th2-like bias, thus contributing to a pregnancy-protecting environment that may be disturbed in recurrent abortions, 37,58 Recently, more subsets of CD4 1 T cells have been characterized at the maternal-fetal interface. There is a balance between the Th1 and Th2 cells, as well as Th17 and regulatory T cells (Tregs) in the firsttrimester human decidua.…”

“…[111][112][113] DCs are associated with vascular growth during the early gestation. 58,105 CXCL12/CXCR4 signalling is important in the regulation of decidual angiogenesis by DCs. Blocking CXCR4…”

“…103,104 It is postulated that extensive crosstalk between placental trophoblasts and DICs, produces angiogenic factors near maternal spiral arteries. 58 Maternal DICs, especially dNK cells and also DCs, play an important role in the immune regulation of trophoblast invasion and uterine spiral arteries remodeling. 105 Although this process is still not well understood, chemokines and their receptors are likely involved in guiding cytotrophoblasts to the decidua and maternal vessels and in attracting immunocompetent cells to the implantation site by either recruitment of VEGF-expressing macrophages or direct stimulation of chemokine receptors on the endothelium.…”

Placentation, maternal–fetal interface, and conceptus loss in swine

“…To date, we have examined expression profiles for important angiogenic, inflammatory and regulatory genes expressed at the M-F interface throughout the length of porcine pregnancy. We observed a shift between type 1 [pro-inflammatory cytokines such as interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), interleukin-2 (IL-2)] and type 2 lymphocytes (anti-inflammatory cytokines such as IL-4, IL-5, IL-6, IL-10) between gd20 and 195 gd50 in pigs, respectively [55]. The major findings of cytokine expression from our laboratory as well as others are summarized in Table 1.…”

“…Physiological similarities to humans makes pig an excellent candidate to provide better understanding in research related to pathology, genetics, gastroenterology, cardiovascular diseases [1] and potentially for xenotrasplantation [2]. According to the Food and Agriculture Organization of the United Nations (FAO), pork was forecasted to be the most 55 widely consumed meat around the world in 2014, amounting to 115.5 million tons (37% of the total consumed meats). High productive and reproductive efficiencies in pigs contribute to the lower cost of pork compared with other livestock meats.…”