The Role of Interleukin-11 in Placentation in Mice (#136)
The placenta forms the interface between the maternal and fetal circulation and is critical for survival and growth of the fetus. Placentation involves trophoblast cell invasion into the decidua to remodel maternal arteries. Interleukin (IL)-11 is critical for human trophoblast cell migration/invasion, critical processes for placentation1. IL11 is critical for uterine decidualization and implantation in mice however its role in placentation has not been investigated. The aim of this study was to examine the effect of IL11 inhibition on placentation in vivo in mice. We immunolocalised IL11 and IL11-receptor(R)-a in mouse implantation sites mid-gestation at days (D) 6, 10 and 13 of pregnancy (D0: day of plug). IL11Ra localised to the maternal endothelial and smooth muscle cells and trophoblast cells in the placenta. IL11 was similarly produced by the decidua, trophoblast cells and spiral arteries. Intraperitoneal injection of a unique PEGylated IL11 antagonist (PEGIL11A) to mice (600µg/application PEGIL11A or PEG control) at 1000h and 1600h on D8 and D9 and 1000h on D10, confirmed differences were evident in the decidua on D11 (late decidualisation). In mice treated on D10-12, morphological differences were evident in the highly vascular placental labyrinth on D13 (mature placenta). The labyrinth structure and fetal blood vessels consisted of fine, closely interacting branches forming a complex labyrinth, in the normal placenta of PEG control mice. PEGIL11A treatment resulted in a less compact labyrinth zone and a-SMA immunostaining confirmed a reduction in the number of fetal vessels in the placenta, as well as altered vessel integrity. Cytokeratin immunostaining (trophoblast specific) revealed a reduction in invasive intrauterine giant trophoblast cells, which produce angiogenic and vasodilatory factors. Our data showed that blocking IL11 during placental formation altered the placental vascularization and placental structure in mice, suggesting IL11 has an important role in placentation in vivo.
- Paiva, P et al. Biology of Reproduction 2009; 80: 301-310.