Utero-Placental Immune Milieu during Normal and Aglepristone-Induced Parturition in the Dog.

Maternal immunotolerance is required for the maintenance of pregnancy, in sharp contrast with the uterine pro-inflammatory activity observed during parturition in several species. Correspondingly, in the dog, increased immune signaling at term has been suggested, but a deeper understanding of the uterine immune milieu is still missing. Thus, the availability of 30 immune-related factors was assessed in utero-placental samples collected during post-implantation (days 18-25 of pregnancy) and mid-gestation (days 35-40) stages, and at the time of prepartum luteolysis. Gene expression and/or protein localization studies were employed. Samples collected from antigestagen (aglepristone)-treated dogs were further analyzed. Progression of pregnancy was associated with the downregulation of IL1β and upregulation of IL10 ( p < 0.05) at mid-gestation. When compared with mid-gestation, a higher availability of several factors was observed at term (e.g., CD206 , CD4 , TLR4 ). However, in contrast with natural parturition, MHCII , CD25 , CCR7 , TNFα , IDO1 and AIF1 were upregulated after aglepristone treatment ( p < 0.05), but not TNFR1 or CCL13 ( p > 0.05). Altogether, these results show an increased immune activity during canine parturition, involving, i.a., M2 macrophages, Treg and Th cells, with strong support for progesterone-mediated immunomodulation. Furthermore, differences between term and induced parturition/abortion could relate to differences in placental maturation towards parturition and/or functional traits of antigestagens.