Maternal Low-Grade Chronic Inflammation and Intrauterine Programming of Health and Disease

Abstract

Overweight and obesity during pregnancy have been associated with increased birth weight, childhood obesity, and noncommunicable diseases in the offspring, leading to a vicious transgenerational perpetuating of metabolic derangements. Key components in intrauterine developmental programming still remain to be identified. Obesity involves chronic low-grade systemic inflammation that, in addition to physiological adaptations to pregnancy, may potentially expand to the placental interface and lead to intrauterine derangements with a threshold effect. Animal models, where maternal inflammation is mimicked by single injections with lipopolysaccharide (LPS) resembling the obesity-induced immune profile, showed increased adiposity and impaired metabolic homeostasis in the offspring, similar to the phenotype observed after exposure to maternal obesity. Cytokine levels might be specifically important for the metabolic imprinting, as cytokines are transferable from maternal to fetal circulation and have the capability to modulate placental nutrient transfer. Maternal inflammation may induce metabolic reprogramming at several levels, starting from the periconceptional period with effects on the oocyte going through early stages of embryonic and placental development. Given the potential to reduce inflammation through inexpensive, widely available therapies, examinations of the impact of chronic inflammation on reproductive and pregnancy outcomes, as well as preventive interventions, are now needed.

Keywords: fetal inflammation; fetal programming; maternal chronic low-grade inflammation; obesity; placental inflammation.

Figure 1

Transgenerational perpetuation of metabolic diseases through maternal low-grade chronic inflammation. The vicious cycle links maternal pregestational chronic low-grade inflammation to feto-placental inflammation with short- and long-term adverse outcomes. TNF: tumor necrosis factor; IL: interleukin; CRP: C-reactive protein; GDM: gestational diabetes mellitus; FGR: fetal growth restriction; IUFD: intra-uterine fetal demise. “↑” means increase; “↓” means decrease; “+” means additional.