UC Irvine

Maternal obesity is a significant risk factor for obstetric complications such as preterm labor, preeclampsia, and chorioamnionitis. Furthermore, pregnant women with obesity are more prone to infections during pregnancy and following postpartum procedures, suggesting a compromised immune system. We therefore hypothesized that the immune adaptations associated with a healthy gestation are disrupted with obesity. Indeed, our analyses suggest that a healthy pregnancy was associated with systemic changes indicative of innate immune activation. Specifically, monocyte responses to LPS were increaed with gestational age in lean subjects, with concomitant enhancement of chromatin accessibility, which poised cells for a greater response. This trajectory was disrupted in pregnant women with obesity resulting in attenuated monocyte responses to LPS. Furthermore, epigenetic, metabolic, and functional measurements strongly support the induction of immunotolerance with pregravid obesity. These findings may explain the increased susceptibility to infections observed during pregnancy and following cesarean delivery in women with obesity.