Maternal inflammation at 0.7 gestation in ewes leads to intrauterine growth restriction and impaired glucose metabolism in offspring at 30 d of age

Fetal programming associated with intrauterine growth restriction (IUGR) leads to lifelong deficits in growth and metabolic function (Hales and Barker, 2013). IUGR arises when fetuses respond to poor in utero conditions by developing adaptations that repartition nutrients to critical tissues and away from skeletal muscle (Yates et al., 2012, 2018). This fetal programming is beneficial in utero but leads to persistent reductions in muscle mass and glucose homeostasis in offspring (DeFronzo et al., 1981). Recent studies by our laboratory in sheep and rats demonstrate that maternal inflammation during gestation induces fetal inflammatory adaptations that impair growth and disrupt muscle glucose metabolism (Cadaret et al., 2017, 2018). IUGR fetal skeletal muscle exhibits indicators of enhanced inflammatory sensitivity, which could disrupt glucose uptake and oxidation (Yates et al., 2016; Cadaret et al., 2018). Enhanced inflammatory responsiveness would help explain growth and metabolic deficits observed in IUGR offspring. We hypothesize that fetal programming induced by maternal inflammation persists in offspring and contributes to impaired growth and glucose metabolism at 30 d. Therefore, the objective of this study was to determine whether sustained maternal inflammation induced by bacterial endotoxin at 0.7 gestation leads to fetal programming that contributes to deficits in growth and glucose metabolism in offspring

Evolution of Thriftiness: An analytical viewpoint

We examine here, using a simple mathematical model, the conditions under which thrifty genes or fetal programming could evolve. Obesity and related disorders are thought to have their roots in metabolic thirftiness that evolved to combat periodic starvation. The failure to detect any thrifty genes and the association of low birth weight with type 2 diabetes, caused a shift in the concept from thrifty gene to thrifty phenotype and fetal programming. This hypothesis assumes that intra-uterine undernutrition programs the body to be thrifty, predicting and preparing for starvation in later life. However, there are reproductive costs associated with thriftiness. Results of the model suggest that under no condition thrifty and non-thrifty genes would co-exist stably in a population. The conditions for evolution of fetal programming are also very restricted. For species with longer life spans, programming for thriftiness is unlikely to evolve if starvation is decided by seasonality or stochastic annual climatic variations since the correlation between intra-uterine and life-time conditions is poor. On the other hand, if starvation is governed by longer periodicity factors such as population oscillations or social hierarchies, there can be better correlation between intra-uterine and life time conditions. Therefore social and population processes are more likely to have selected for fetal programming rather than seasonal and climatic “feast and famine” conditions. Since social and population processes can have cues other than diet, these cues may also influence the incidence of obesity related disorders as some recent evidence suggest

Can Thrifty Gene(s) or Predictive Fetal Programming for Thriftiness Lead to Obesity?

Obesity and related disorders are thought to have their roots in metabolic “thriftiness” that evolved to combat periodic starvation. The association of low birth weight with obesity in later life caused a shift in the concept from thrifty gene to thrifty phenotype or anticipatory fetal programming. The assumption of thriftiness is implicit in obesity research. We examine here, with the help of a mathematical model, the conditions for evolution of thrifty genes or fetal programming for thriftiness. The model suggests that a thrifty gene cannot exist in a stable polymorphic state in a population. The conditions for evolution of thrifty fetal programming are restricted if the correlation between intrauterine and lifetime conditions is poor. Such a correlation is not observed in natural courses of famine. If there is fetal programming for thriftiness, it could have evolved in anticipation of social factors affecting nutrition that can result in a positive correlation

Fetal programming and epigenetics

Accumulating evidence suggests that the intrauterine environment can have an impact on long-term offspring health, so-called �fetal programming�. A number of environmental stressors have been studied in humans including maternal nutrition, smoking, substance misuse and mental illness. Although various biological mechanisms are likely to underpin fetal programming effects, there has been a particular focus on epigenetic modifications as potential mediators of observed associations between early environmental exposures and later health outcomes. In this review, we give an overview of evidence supporting a role for epigenetics in fetal programming, highlighting key human and animal studies. We also discuss challenges for research in this area, along with recommendations for future work, and potential therapeutic applications

Fetal Programming in Rheumatoid Arthritis

__Abstract__ Rheumatoid arthritis (RA) is a chronic, systemic, inflammatory, autoimmune disease mainly affecting synovial tissues, which can lead to severe morbidity and progressive joint destruction resulting in deformations and disability. Other important outcomes include extra-articular features and comorbidities, like vasculitis, cardiac disease and infections. RA affects approximately 1% of the adult population and each year, 5 to 50 per 100.000 persons develop this condition. Women are affected two to three times more often than men. The age of onset in women is usually between 40 and 50 years, but it often affects women of childbearing age

Effects of Gestational Dietary Intake on Calf Growth and Early Feedlot Performance of Offspring

Fetal programming is a relatively new and quickly growing field of research in the livestock industry. The concept of fetal programming is simply defined as the effects a change in maternal nutritional intake has on offspring, whether it be a genetic or physical change. The intention of this study was to specifically look at the effects of nutrient restriction of cows during the second trimester of gestation on the growth and performance of the resulting calves. In this study, thirty-two cows of predominantly angus influence from the Utah state university herd were chosen, naturally bred to a pure bred angus sire, and then allocated into two treatments: maintenance and restricted. These groups were treated uniformly for first and third trimesters of gestation, while in the second trimester, they were managed in a way that the maintenance group maintained a greater level of body condition and weight compared with the restricted group. Calf growth and performance was measured and compared for effects of fetal programming. Previous studies in beef found positive effects on carcass characteristics. However, little work has been done to ensure that fetal programming is not detrimental to calves early in life. Though this study did find that nutrient restriction resulted in more excitable cattle, no negative effects caused by programming were found in growth and performance of the offspring

Fetal Programming in Maternal Obesity

The project described was supported by the Nebraska Center for Prevention ofObesity Diseases, the National Institute of General Medical Sciences Grant(P20GM104320 to SKN), the Nebraska Agricultural Experimental Station with fundingfrom the Hatch Act (Accession Number 1014526 to SKN) through the United StatesDepartment of Agriculture, National Institute of Food and Agriculture (USDA-NIFA), theNebraska Tobacco Settlement Biomedical Research Development Funds and theUniversity of Nebraska-Lincoln. The contents of this manuscript are solely theresponsibility of the authors and does not necessarily represent the official views of theNational Institutes of Health