We recently reported augmentation of lipid peroxidation products in the liver of intrauterine growth-restricted (IUGR) piglets fed a high load of Maillard reaction products (MRPs) during suckling period. The underlying mechanisms of MRPs effects remain unknown. Here, we studied the long-term impact of MRPs exposure on liver oxidative status of IUGR juvenile pigs. Livers of 54-day-old pigs suckled with formula containing either a high (HHF, n=8) or a low (LHF: n=8) load of MRPs were analyzed for protein carbonylation levels , activities and messenger RNA (mRNA) expression of glutathione (GSH) and main antioxidant regulators of redox homeostasis [Superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) were measured. In addition, mRNA levels of miRNA-21 and miRNA-155 were measured. The liver of HHF group exhibited a high level of lipid peroxidation with significantly increased expression and activity of SOD. Further in liver of HHF group, CAT activity was decreased as compared with LHF group, though with comparable total protein carbonyl contents, GSH contents, and expression of GPx and microRNAs (miRNA-21 and miRNA-155). Our findings suggest that the potential mechanism of MRPs-mediated oxidative stress programming in liver of IUGR piglets may occur via impairment of antioxidant defenses.

Early nutrition may have long-lasting metabolic impacts in adulthood. Even though breast milk is the gold standard, most infants are at least partly formula-fed. Despite obvious improvements, infant formulas remain perfectible to reduce the gap between breastfed and formula-fed infants. Improvements such as reducing the protein content, modulating the lipid matrix and adding prebiotics, probiotics and synbiotics, are discussed regarding metabolic health. Numerous questions remain to be answered on how impacting the infant formula composition may modulate the host metabolism and exert long-term benefits. Interactions between early nutrition (composition of human milk and infant formula) and the gut microbiota profile, as well as mechanisms connecting gut microbiota to metabolic health, are highlighted. Gut microbiota stands as a key actor in the nutritional programming but additional well-designed longitudinal human studies are needed.

The developmental origin of health and disease highlights the importance of the period of the first 1000 days (from the conception to the 2 years of life). The process of the gut microbiota establishment is included in this time window. Various perinatal determinants, such as cesarean section delivery, type of feeding, antibiotics treatment, gestational age or environment, can affect the pattern of bacterial colonization and result in dysbiosis. The alteration of the early bacterial gut pattern can persist over several months and may have long-lasting functional effects with an impact on disease risk later in life. As for example, early gut dysbiosis has been involved in allergic diseases and obesity occurrence. Besides, while it was thought that the fetus developed under sterile conditions, recent data suggested the presence of a microbiota in utero, particularly in the placenta. Even if the origin of this microbiota and its eventual transfer to the infant are nowadays unknown, this placental microbiota could trigger immune responses in the fetus and would program the infant’s immune development during fetal life, earlier than previously considered. Moreover, several studies demonstrated a link between the composition of placental microbiota and some pathological conditions of the pregnancy. All these data show the evidence of relationships between the neonatal gut establishment and future health outcomes. Hence, the use of pre- and/or probiotics to prevent or repair any early dysbiosis is increasingly attractive to avoid long-term health consequences.

Intrauterine growth restriction (IUGR) has been identified as a risk factor for adult chronic kidney disease (CKD), including hypertension (HTN). Accelerated postnatal catch-up growth superimposed to IUGR has been shown to further increase the risk of CKD and HTN. Although the impact of excessive postnatal growth without previous IUGR is less clear, excessive postnatal overfeeding in experimental animals shows a strong impact on the risk of CKD and HTN in adulthood. On the other hand, food restriction in the postnatal period seems to have a protective effect on CKD programming. All these effects are mediated at least partially by the activation of the renin–angiotensin system, leptin and neuropeptide Y (NPY) signaling and profibrotic pathways. Early nutrition, especially in the postnatal period has a significant impact on the risk of CKD and HTN at adulthood and should receive specific attention in the prevention of CKD and HTN.

Epidemiological and experimental observations tend to prove that environment, lifestyle or nutritional challenges influence heart functions together with genetic factors. Furthermore, when occurring during sensitive windows of heart development, these environmental challenges can induce an ‘altered programming’ of heart development and shape the future heart disease risk. In the etiology of heart diseases driven by environmental challenges, epigenetics has been highlighted as an underlying mechanism, constituting a bridge between environment and heart health. In particular, micro-RNAs which are involved in each step of heart development and functions seem to play a crucial role in the unfavorable programming of heart diseases. This review describes the latest advances in micro-RNA research in heart diseases driven by early exposure to challenges and discusses the use of micro-RNAs as potential targets in the reversal of the pathophysiology.

Experimental data have suggested that some contaminants in the environment may increase the risk of obesity. Infants can be exposed to chemicals either prenatally, by trans-placental passage of chemicals, or postnatally by their own diet and by other external pathways (air inhalation, dust, hand-to-mouth exposure) after birth. To provide a review of epidemiological evidence on the association between prenatal exposure to chemicals and prenatal and postnatal growth, we present the literature from systematic review articles and international meta-analyses, when available, or recent research articles when summarizing articles were not available. The most studied contaminants in this field were persistent organic pollutants (e.g. organochlorinated pesticides, polychlorinated biphenyls), non-persistent pollutants (e.g. phthalates, bisphenol A), toxic heavy metals (i.e. cadmium, lead and mercury), arsenic, mycotoxins and acrylamide. Mounting evidence suggests that child’s growth may be associated with prenatal or postnatal exposures to environmental contaminants. Improving exposure assessment and studying the contaminants as mixtures should allow to gain knowledge about the environmental determinants of growth and obesity.

Non-communicable diseases (NCDs) are a major problem as they are the leading cause of death and represent a substantial economic cost. The ‘Developmental Origins of Health and Disease Hypothesis’ proposes that adverse stimuli at different life stages can increase the predisposition to these diseases. In fact, adverse in utero programming is a major origin of these diseases due to the high malleability of embryonic development. This review provides a comprehensive analysis of the scientific literature on in utero programming and NCDs highlighting potential medical strategies to prevent these diseases based upon this programming. We fully address the concept and mechanisms involved in this programming (anatomical disruptions, epigenetic modifications and microbiota alterations). We also examine the negative role of in utero programming on the increased predisposition of NCDs in the offspring, which introduces the passive medical approach that consists of avoiding adverse stimuli including an unhealthy diet and environmental chemicals. Finally, we extensively discuss active medical approaches that target the causes of NCDs and have the potential to significantly and rapidly reduce the incidence of NCDs. These approaches can be classified as direct in utero programming modifications and personalized lifestyle pregnancy programs; they could potentially provide transgenerational NCDs protection. Active strategies against NCDs constitute a promising tool for the reduction in NCDs.

There is limited evidence on the association between maternal preconception body mass index (BMI) trajectories and pregnancy complications and child development. This study examined the relationships of maternal BMI trajectories, diabetes and hypertensive disorders during pregnancy and offspring’s childhood physical and cognitive development. Data were from the Australian Longitudinal Study on Women’s Health and the Mothers and their Children’s Health study (n=771). Women’s preconception BMI trajectories were identified using group-based trajectory modelling. Children’s physical and cognitive development (up to the average age of 5 years) were obtained from the Ages and Stages Questionnaire (suspected gross motor delay) and the Australian Early Development Census (AEDC). Generalized estimating equation models, adjusted for maternal sociodemographic and lifestyle factors, were used for analyses. Three distinct BMI trajectories were identified (normative, chronically overweight and chronically obese). Children born to chronically obese women were more likely to be classified as developmentally vulnerable/at-risk on AEDC domains; gross and fine motor skills [risk ratio (RR)=1.64, 95% confidence interval (CI): 1.04, 2.61] and communication skills and general knowledge (RR=1.71, 95% CI: 1.09, 2.68). They also had an elevated risk of suspected gross motor delay (RR=2.62, 95% CI: 1.26, 5.44) compared with children born to women with a normative BMI trajectory. Maternal diabetes or hypertensive disorders during pregnancy were not associated with child outcomes. Maternal preconception BMI trajectories were associated with poorer childhood development. This study finding underscores the importance of excessive weight gain prevention throughout the reproductive stage of life.

Exposure to prenatal hypoxia in rats leads to intrauterine growth restriction (IUGR), decreases fetal cardiomyocyte proliferation and increases the risk to develop cardiovascular diseases (CVD) later in life. The tumor necrosis factor-related weak inducer of apoptosis (TWEAK) induces cardiomyocyte proliferation through activation of the fibroblast growth factor-inducible molecule 14 (Fn-14) receptor. The TWEAK/Fn-14 pathway becomes quiescent shortly after birth, however, it becomes upregulated with CVD; suggesting that it could be a link between the increased susceptibility to CVD in pregnancies complicated by hypoxia/IUGR. We hypothesized that offspring exposed to prenatal hypoxia will exhibit reduced cardiomyocyte proliferation due to reduced Fn-14 expression and that the TWEAK/Fn-14 pathway will be expressed in those adult offspring. We exposed pregnant Sprague Dawley rats to control (21% oxygen) or hypoxic (11% oxygen) conditions from gestational days 15 to 21. Ventricular cardiomyocytes were isolated from male and female, control and hypoxic offspring at postnatal day 1. Proliferation was assessed in the presence or absence of r-TWEAK (72 h, 100 ng/ml). Prenatal hypoxia was not associated with differences in Fn-14 protein expression in either male or female offspring. Cardiomyocytes from prenatal hypoxic male, but not female, offspring had decreased proliferation compared with controls. Addition of r-TWEAK increased cardiomyocyte proliferation in all offspring. In adult offspring of all groups, the TWEAK/Fn-14 pathway was not detectable. Cardiomyocyte proliferation was reduced in only male offspring exposed to prenatal hypoxia but this was not due to changes in the Fn-14 pathway. Studies addressing other pathways associated with CVD and prenatal hypoxia are needed.

Exposure to maternal over-nutrition in utero is linked with developmental programming of obesity, metabolic syndrome and cardiovascular disease in offspring, which may be exacerbated by postnatal high-fat (HF) diet. Skeletal muscle mitochondrial function contributes to substrate metabolism and is impaired in metabolic disease. We examined muscle mitochondrial respiration in male and female mice exposed to maternal HF diet in utero, followed by postweaning HF diet until middle age. After in utero exposure to maternal control (Con) or HF diet (45% kcal fat; 39.4% lard, 5.5% soybean oil), offspring were weaned to Con or HF, creating four groups: Con/Con (male/female (m/f), n=8/8), Con/HF (m/f, n=7/4), HF/Con (m/f, n=9/6) and HF/HF (m/f, n=4/4). Oxidative phosphorylation (OXPHOS) and electron transfer system (ETS) capacity were measured in permeabilized gastrocnemius bundles. Maternal HF diet increased fasting glucose and lean body mass in males and body fat percentage in both sexes (P⩽0.05). Maximal adenosine diphosphate-stimulated respiration (complex I OXPHOS) was decreased by maternal HF diet in female offspring (−21%, P=0.053), but not in male (−0%, P>0.05). Sexually divergent responses were exacerbated in offspring weaned to HF diet. In females, OXPHOS capacity was lower (−28%, P=0.041) when weaned to high-fat (HF/HF) v. control diet (HF/Con). In males, OXPHOS (+33%, P=0.009) and ETS (+42%, P=0.016) capacity increased. Our data suggest that maternal lard-based HF diet, rich in saturated fat, affects offspring skeletal muscle respiration in a sex-dependent manner, and these differences are exacerbated by HF diet in adulthood.

In utero exposure to the ubiquitous plasticizer, bisphenol A (BPA) is associated with offspring obesity. As adipogenesis is a critical factor contributing to obesity, we determined the effects of in vivo maternal BPA and in vitro BPA exposure on newborn adipose tissue at the stem-cell level. For in vivo studies, female rats received BPA before and during pregnancy and lactation via drinking water, and offspring were studied for measures of adiposity signals. For in vitro BPA exposure, primary pre-adipocyte cell cultures from healthy newborns were utilized. We studied pre-adipocyte proliferative and differentiation effects of BPA and explored putative signal factors which partly explain adipose responses and underlying epigenetic mechanisms mediated by BPA. Maternal BPA-induced offspring adiposity, hypertrophic adipocytes and increased adipose tissue protein expression of pro-adipogenic and lipogenic factors. Consistent with in vivo data, in vitro BPA exposure induced a dose-dependent increase in pre-adipocyte proliferation and increased adipocyte lipid content. In vivo and in vitro BPA exposure promotes the proliferation and differentiation of adipocytes, contributing to an enhanced capacity for lipid storage. These findings reinforce the marked effects of BPA on adipogenesis and highlight the susceptibility of stem-cell populations during early life with long-term consequence on metabolic homeostasis.