Functional and genomic adaptations of blood monocytes to pregravid obesity during pregnancy

Pregravid obesity is associated with several adverse maternal health outcomes, such as increased risk of infection, suggesting an altered immunological state. However, the mechanisms by which obesity disrupts the pregnancy immune clock'' are still unknown. Here, we profiled circulating immune mediators, immune cell subset frequencies, and peripheral immune responses during the first and third trimesters of pregnancy in lean and obese mothers. While both Th1 and Th2 cytokines were elevated with pregnancy regardless of BMI, obese subjects had dysregulated myeloid factors in circulation at term. Pregnancy in lean subjects was associated with enhanced monocyte activation, augmented chromatin accessibility at inflammatory loci, and heightened responses to LPS. Pregravid obesity disrupted this trajectory, resulting in a lack of transcriptional, epigenetic, and metabolic changes strongly suggesting a skewing toward innate immune tolerance. These findings provide novel insight into the increased susceptibility to infections in women with obesity during pregnancy and following cesarean delivery.

Automated summary

Pregravid obesity is associated with adverse maternal health outcomes, with altered immunological state. Both lean and obese mothers showed elevated Th1 and Th2 cytokines during pregnancy, but obese subjects had dysregulated myeloid factors in circulation. Lean pregnancy was associated with enhanced immune response, while obese pregnancy showed signs of innate immune tolerance.