Reproduction Abstracts

Introduction: Placentation involves trophoblast cell invasion into the decidua to remodel maternal arteries. Interleukin (IL)-11 is critical for human trophoblast cell migration/invasion in vitro, however its role in placentation in vivo has not been investigated. We hypothesised that IL11 plays a critical role in trophoblast function during placentation. The aim of this study was to examine the effect of IL11 inhibition on placentation in mice.

Methods: IL11 and IL11-receptor(R)-α were immunolocalised in mouse implantation sites throughout gestation (n=4/time-point). To determine the role of IL11 during placentation, C57BL/6J mice were administered with a unique PEGylated IL11 antagonist (PEGIL11A; n=4/group, 600 μg/application PEGIL11A or PEG control) twice daily at days (D)10–13, or 10–17 of pregnancy (D0: day of plug). Implantation sites collected at D13 or 17 were stained with haematoxylin and eosin, cytokeratin (trophoblast marker), isolectin-B4 and α-SMA (vascular markers).

Results: IL11 and IL11Rα localised to the maternal decidua and highly vascularized placental labyrinth, mid-gestation of pregnancy in mice. IL11Rα localised to fetal endothelial and trophoblast cells. IL11 was produced by trophoblast cells. IL11 inhibition resulted in dysregulated placental labyrinth structure at D13, with a significant reduction in trophoblast staining area (25.25%±1.98 vs control 37.58%±2.13; P<0.01) and morphologically altered vascular spaces. PEGIL11A treatment from D10–17 lead to altered placentas and an edematous fetal phenotype compared to controls.

Conclusion: Our data showed that blocking IL11 during placentation altered placental trophoblasts and vasculature, demonstrating that placental derived IL11 is required for normal placentation. This study highlights the important role of IL11 in placentation in vivo.