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.

Primary HSV-2 Infection in Early Pregnancy Results in Transplacental Viral Transmission and Dose-Dependent Adverse Pregnancy Outcomes in a Novel Mouse Model

“…Alternately, induction of preterm birth by mid-pregnancy administration of heat-killed E. coli resulted in significantly increased levels of IL-1α, IL-1β, and IL-6 in the uterus, while TNF-α levels were similar to controls [62]. Additionally, low-grade inflammation in the placenta, as observed with low doses of HSV-2 in our study, has been observed in pregnancies complicated by maternal obesity that result in adverse pregnancy outcomes, including congenital abnormalities and fetal macrosomia, in the absence of more severe outcomes [63,64]. Further, in a study conducted using first trimester placental tissues obtained from normal pregnancies and spontaneous abortions, only placental tissues from spontaneous abortions were associated with unstimulated production of inflammatory mediators [65].…”

Adherence to the Mediterranean diet during pregnancy is associated with lower odds of excessive gestational weight gain and postpartum weight retention: results of the Mother-Infant Study Cohort

“…More specifically, a higher adherence to the MD was associated with the prevention of GDM (26,27) , decreasing the risk of compromised fetal growth, prematurity, neural tube defects, asthma, allergy as well as a decrease in the cardio-metabolic risks for both mother and child (28,29) . Pregnancy has been considered as a physiological low-grade systemic inflammatory status with the placenta producing a range of inflammatory cytokines (30) . The protective effect of the MD against metabolic abnormalities during pregnancy could be due to the fact that this pattern is rich in antioxidants nutrients (vegetables and fruits) or antioxidant phenols (olive oil and red wine).…”

Role of Inflammaging on the Reproductive Function and Pregnancy

“…Obesity plays a pivotal role in the pathogenesis of inflammaging, since the massive expansion of the adipose tissue, as a highly active endocrine organ, affects immune cell profile, deranges inflammatory cytokines production, and finally impairs metabolic function [11]. Such a metabolic dependent pro inflammatory background, the so-called meta-inflammation, in turn, influences the metabolism itself leading to increased oxidative stress and insulin resistance [12].…”

“…Once pregnancy is established, the modulation of the maternal immune system is crucial to the embryo development and pregnancy maintenance [68]. Despite the historical idea that maternal systemic immune suppression is essential for fetal acceptance, a more complex feto-maternal immune interaction has been recently described, with both intrauterine and systemic inflammation as pivotal components of healthy pregnancies [11]. In this scenario, several pregestational maternal stressors (i.e., obesity, chronic comorbidities, advanced maternal age, malnutrition, smoking) have been associated with maladaptive changes in pregnancy and obstetric complications with disrupted intrauterine environment and fetal development.…”