Placental interleukin 1β signaling in canine pregnancy: differential effects during and after decidualization in vitro

In brief: The role of inflammation in the regulation of pregnancy remains poorly understood in dogs. Findings from this study propose the involvement of IL1β signaling during early embryo-maternal interactions in the dog, while in vitro effects suggest it may disrupt decidual cell function in the canine mature placenta. Although implantation and parturition are associated with pro-inflammatory signals, inflammatory responses in the mature placenta frequently lead to pregnancy loss. Indeed, uterine inflammatory/infectious diseases are major causes of infertility and pregnancy loss in dogs. The pro-inflammatory interleukin (IL)-1β is increased during canine placentation and downregulated in mature placentae during healthy pregnancies but is enriched in the placenta during infectious events. Furthermore, canine pregnancy success is linked with decidual cells, the only placental cells expressing the nuclear progesterone receptor. This study assessed utero-placental abundance of IL1β receptor 1 (IL1R1) throughout canine pregnancy and possible modulatory effects of IL1β on decidualization. The mRNA levels of IL1R1 were increased in mature mid-gestation placentae and at term (P < 0.05). Immunohistochemistry co-localized IL1β and IL1R1 in the trophoblast during early placentation, implicating IL1β-signaling in early embryo-maternal communication. In the mature placenta, IL1R1 was localized, i.a. in decidual cells. In vitro, IL1β had low modulatory effects on PGE2- and/or P4-stimulated dog uterine stromal (DUS) cells, implying a relatively weak impact of this interleukin in the decidualization process. However, in DUS cells decidualized with cAMP, IL1β decreased transcriptional amounts of selected decidualization markers IGF1, PTGS2 and PTGES, as well as ECM1 and TIMP2 (P < 0.001). Transcriptional and protein availabilities of CX43, a gap junction component, were also decreased by IL1β (P < 0.001). These findings support a dual role for IL1β in canine pregnancy: involvement in early embryo-maternal communication during its establishment and disturbing placental homeostasis by disrupting decidual cell function in fully developed placenta.