Maternal Diet-Induced Excess Adiposity in Mice Disrupts Mid-Gestation Decidual Immune and Vascular Homeostasis Without Impairing Spiral Artery Remodeling.

AIM: Maternal excess adiposity (i.e., overweight/obesity) is linked to impaired uteroplacental perfusion, compromised placental development, and increased risk of adverse pregnancy outcomes. Inflammation and immune dysregulation accompanying excess adiposity may disrupt leukocyte-mediated tissue remodeling and immunoregulation, contributing to placental dysfunction. However, the impacts of excess adiposity on populations of innate lymphoid cells and macrophages orchestrating these processes, and on the decidual microenvironment, remain understudied. Here, we used a mouse model of high-fat, high-sucrose (HFHS) diet-feeding to study the impacts of excess adiposity on decidual immune dynamics during placental development. METHODS: Uteroplacental tissues were collected at mid-gestation (E10.5) from mice fed a control chow (CON) or HFHS diet before and during pregnancy. Multicolour flow cytometry was used to profile decidual leukocyte composition. Spiral artery remodeling was measured using (immuno)histochemistry. Multiplex immunoassays were used to compare systemic and decidual cytokine and growth factor levels. Comparative gene expression was measured in placental tissues using a NanoString nCounter array. RESULTS: HFHS pregnancies had elevated decidual leukocyte abundance, with increased tissue-resident and conventional-like NK cells, and MHC-II(+) macrophages. This was not associated with abnormal spiral artery remodeling but coincided with increased decidual proinflammatory cytokine and chemokine expression, and greater elevations in mediators of angiogenesis, endothelial activation, and coagulation. Despite this, placental gene expression was largely unaltered at mid-gestation. CONCLUSION: These findings point towards decidual vascular inflammation and dysregulated angiogenesis during early placentation in pregnancies complicated by excess adiposity. This may stem from or induce shifts in resident immune cells, contributing to later placental dysfunction.