Interleukin-11 alters placentation and causes preeclampsia features in mice

• DOI: 10.1073/pnas.1515076112
• Publication Date: 2015-12-12T03:49:00Z
• Authors: Amy L. Winship; Kaori Koga; Ellen Menkhorst; Michelle Van Sind...; Katarzyna Rainczuk; Miwako Nagai; Carly Cuman; Joanne Yap; Jian-Guo Zhang; David Simmons; Morag J. Young; Evdokia Dimitriadis
• Keywords: Male; 0301 basic medicine; Placenta; Blotting, Western; Enzyme-Linked Immunosorbent Assay; 03 medical and health sciences; Pre-Eclampsia; Pregnancy; Decidua; Animals; Humans; Pregnancy-Associated Plasma Protein-A; Receptors, Interleukin-11; Reverse Transcriptase Polymerase Chain Reaction; Trophoblast; Gene Expression Regulation, Developmental; Interleukin-11; Immunohistochemistry; Placentation; Recombinant Proteins; Mice, Inbred C57BL; 1000 General; Cytokines; Female; RNA Interference

Significance

Preeclampsia is an insidious disease, unique to humans, affecting ∼8% of pregnancies. There are no early detection tests or pharmacological treatments. Impaired placentation is widely accepted to contribute to the pathogenesis. However, the mechanisms remain elusive, given the complications of studying first-trimester placental development in women. A major limitation for the study of new treatments is the lack of available animal models that recapitulate the full spectrum of preeclampsia features. We have developed a mouse model characterized by elevated levels of the cytokine Interleukin-11 (IL11). This study provides evidence of a novel pathway causative of preeclampsia features in vivo . It also provides a novel in vivo mouse model that is useful for preclinical studies to test potential therapeutics.