Based on the Developmental Origin of Health and Disease concept, maternal undernutrition has been shown to sensitize adult offspring to metabolic pathologies such as obesity. Using a model of maternal 70% food restriction in pregnant female rats throughout gestation (called FR30), we previously reported that obesity-prone adult male rat offspring displayed hyperleptinemia with modifications in leptin and leptin receptor messenger RNA (mRNA) levels in white adipose tissue (WAT). Apelin is a member of the adipokine family that regulates various aspects of energy metabolism and WAT functionality. We investigated whether apelin and its receptor APJ could be a target of maternal undernutrition. Adult male rat offspring from FR30 dams showed increased plasma apelin levels and apelin gene expression in WAT. Post-weaning high-fat diet led to marked increase in APJ mRNA and protein levels in offspring’s WAT. We demonstrate that maternal undernutrition and post-weaning diet have long-term consequences on the apelinergic system of adult male rat offspring.

Abundant evidence exists linking maternal and paternal environments from pericopconception through the postnatal period to later risk to offspring diseases. This concept was first articulated by the late Sir David Barker and as such coined the Barker Hypothesis. The term was then mutated to Fetal Origins of Adult Disease and finally broadened to developmental origins of adult health and disease (DOHaD) in recognition that the perinatal environment can shape both health and disease in resulting offspring. Developmental exposure to various factors, including stress, obesity, caloric-rich diets and environmental chemicals can lead to detrimental offspring health outcomes. However, less attention has been paid to date on measures that parents can take to promote the long-term health of their offspring. In essence, have we neglected to consider the ‘H’ in DOHaD? It is the ‘H’ component that should be of primary concern to expecting mothers and fathers and those seeking to have children. While it may not be possible to eliminate exposure to all pernicious factors, prevention/remediation strategies may tip the scale to health rather than disease. By understanding disruptive DOHaD mechanisms, it may also illuminate behavioral modifications that parents can adapt before fertilization and throughout the neonatal period to promote the lifelong health of their male and female offspring. Three possibilities will be explored in the current review: parental exercise, probiotic supplementation and breastfeeding in the case of mothers. The ‘H’ paradigm should be the focus going forward as a healthy start can indeed last a lifetime.

The field of Developmental Origins of Health and Disease (DOHaD) seeks to understand the relationships between early-life environmental exposures and long-term health and disease. Until recently, the molecular mechanisms underlying these phenomena were poorly understood; however, epigenetics has been proposed to bridge the gap between the environment and phenotype. Epigenetics involves the study of heritable changes in gene expression, which occur without changes to the underlying DNA sequence. Different types of epigenetic modifications include DNA methylation, post-translational histone modifications and non-coding RNAs. Increasingly, changes to the epigenome have been associated with early-life exposures in both humans and animal models, offering both an explanation for how the environment may programme long-term health, as well as molecular changes that could be developed as biomarkers of exposure and/or future disease. As such, epigenetic studies in DOHaD hold much promise; however, there are a number of factors which should be considered when designing and interpreting such studies. These include the impact of the genome on the epigenome, the tissue-specificity of epigenetic marks, the stability (or lack thereof) of epigenetic changes over time and the importance of associating epigenetic changes with changes in transcription or translation to demonstrate functional consequences. In this review, we discuss each of these key concepts and provide practical strategies to mitigate some common pitfalls with the aim of providing a useful guide for future epigenetic studies in DOHaD.

Although the use of donor sperm as a treatment modality for male infertility has become common place, the health outcomes for those conceived has been poorly studied. A structured search of the literature using PubMed, EMBASE and Cochrane Reviews was performed to investigate the health outcomes of offspring conceived from donor sperm. Eight studies were eligible and included in the review, and of these, three were included in a meta-analysis. Meta-analysis of clinical outcomes showed that donor sperm neonates are not at increased risk of being born of low birth weight (<2500 g), preterm (<37 weeks) or with increased incidences of birth defects, than spontaneously conceived neonates.

Zinc is an essential micronutrient for the development of the fetal renal, cardiovascular and metabolic systems; however, there is limited evidence of its effects on the postnatal cardiometabolic function. In this study, we evaluated the effect of maternal zinc supplementation during pregnancy on the cardiometabolic profile of the offspring in childhood. A total of 242 pregnant women were randomly assigned to receive a daily supplement containing iron+folic acid with or without zinc. A follow-up study was conducted when children of participating mothers were 4.5 years of age to evaluate their cardiometabolic profile, including anthropometric measures of body size and composition, blood pressure, lipid profile and insulin resistance. No difference in measures of child cardiometabolic risk depending on whether mothers received supplemental zinc during pregnancy. Our results do not support the hypothesis that maternal zinc supplementation reduces the risk of offspring cardiometabolic disease.

Bisphenol-A (BPA) is a widely used endocrine-disrupting chemical. Prenatal exposure to BPA is known to affect birth weight, but its impact on the cardiovascular system has not been studied in detail. In this study, we investigated the effects of prenatal BPA treatment and its interaction with postnatal overfeeding on the cardiovascular system. Pregnant sheep were given daily subcutaneous injections of corn oil (control) or BPA (0.5 mg/kg/day in corn oil) from day 30 to day 90 of gestation. A subset of female offspring of these dams were overfed to increase body weight to ~30% over that of normal fed controls. Cardiovascular function was assessed using non-invasive echocardiography and cuff blood pressure (BP) monitoring at 21 months of age. Ventricular tissue was analyzed for gene expression of cardiac markers of hypertrophy and collagen at the end of the observation period. Prenatal BPA exposure had no significant effect on BP or morphometric measures. However, it increased atrial natriuretic peptide gene expression in the ventricles and reduced collagen expression in the right ventricle. Overfeeding produced a marked increase in body weight and BP. There were compensatory increases in left ventricular area and internal diameter. Prenatal BPA treatment produced a significant increase in interventricular septal thickness when animals were overfed. However, it appeared to block the increase in BP and left ventricular area caused by overfeeding. Taken together, these results suggest that prenatal BPA produces intrinsic changes in the heart that are capable of modulating morphological and functional parameters when animals become obese in later life.

Maternal diet-induced obesity can cause detrimental developmental origins of health and disease in offspring. Perinatal exposure to a high-fat diet (HFD) can lead to later behavioral and metabolic disturbances, but it is not clear which behaviors and metabolic parameters are most vulnerable. To address this critical gap, biparental and monogamous oldfield mice (Peromyscus polionotus), which may better replicate most human societies, were used in the current study. About 2 weeks before breeding, adult females were placed on a control or HFD and maintained on the diets throughout gestation and lactation. F1 offspring were placed at weaning (30 days of age) on the control diet and spatial learning and memory, anxiety, exploratory, voluntary physical activity, and metabolic parameters were tested when they reached adulthood (90 days of age). Surprisingly, maternal HFD caused decreased latency in initial and reverse Barnes maze trials in male, but not female, offspring. Both male and female HFD-fed offspring showed increased anxiogenic behaviors, but decreased exploratory and voluntary physical activity. Moreover, HFD offspring demonstrated lower resting energy expenditure (EE) compared with controls. Accordingly, HFD offspring weighed more at adulthood than those from control fed dams, likely the result of reduced physical activity and EE. Current findings indicate a maternal HFD may increase obesity susceptibility in offspring due to prenatal programming resulting in reduced physical activity and EE later in life. Further work is needed to determine the underpinning neural and metabolic mechanisms by which a maternal HFD adversely affects neurobehavioral and metabolic pathways in offspring.

Emerging evidence highlights the far-reaching consequences of high-fat diet (HFD) and obesity on kidney morphological and functional disorders. In the present study, we aim to evaluate the effects of early HFD intake on renal function and morphology in maternal protein-restricted offspring (LP). LP and normal protein-intake offspring (NP) were fed HFD (LPH and NPH, respectively) or standard rodent (LPN and NPN) diet from the 8th to 13th week of age. Blood pressure, kidney function, immunohistochemistry and scanning electron microscopy were analyzed. Increased total cholesterol and low-density lipoprotein serum levels were observed in LPH offspring. The adiposity index was reduced in the (LPN) group and, conversely, increased in the NPH and LPH groups. Blood pressure was higher beyond the 10th week of age in the LPH group compared with the other groups. Decreased urinary sodium excretion was observed in LP offspring, whereas the HFD-treated groups presented a decreased urine pH in a time-dependent fashion. The LPN, NPH and LPH groups showed increased expression of type 1 angiotensin II (AngII) receptor (AT1R), TGF-β1, collagen and fibronectin in the kidneys. Moreover, the adult fetal-programmed offspring showed pronounced effacement of the podocyte foot process associated with the rupture of cell membranes and striking urinary protein excretion, exacerbated by HFD treatment. To the best of our knowledge, this is the first study demonstrating that young fetal-programmed offspring submitted to long-term HFD intake have increased susceptibility to renal structural and functional disorders associated with an accentuated stage of fibrosis and tubular dysfunction.

Maternal treatment with dexamethasone (Dex) in threatening preterm delivery alters activities at the hypothalamic–pituitary–adrenal axis in the offspring. This alteration may interfere with reproductive function. The impact of gestational Dex exposure on male reproductive function of the offspring was investigated. A total of 25 pregnant rats randomly assigned to five groups (n=5) were treated with normal saline (control), Dex (100 μg/kg/day sc) during gestation days (GD) 1–7, 8–14, 15–21 and 1–21, respectively. Birth weight, anogenital distance (AGD), pubertal age, sperm parameters, hormonal profile and histopathology of testis and epididymis were determined in the F1 and F2 offspring. Results showed a significant increase (P<0.05) in pubertal age, serum corticosterone and gonadotropin-releasing hormone (GnRH) levels in the male offspring of DexGD 15–21 and 1–21 groups and a significant decrease (P<0.05) in serum testosterone, luteinizing hormone, birth weight and AGD at birth in the male F1 offspring. In the F2 offspring, there was a significant reduction (P<0.05) in serum corticosterone, testosterone, follicle-stimulating hormone and GnRH when compared with the control. Dex treatment at GD 15–21 and 1–21 significantly reduced (P<0.05) sperm motility and normal morphology in the F1 and F2 offspring. Maternal Dex treatment in rats during late gestation may disrupt sexual development markers in the F1 and F2 male offspring.

Previous research has shown that childhood body size is associated with blood pressure in adulthood, and that early and rapid growth rates are correlated with adverse cardiovascular outcomes. Our objectives are to estimate associations between childhood body size growth parameters and adult blood pressure, and to examine the effect of early attainment of critical growth milestones on adult blood pressure, relative to normal or late attainment. Lifetime height and body mass index (BMI) measurements in childhood, and systolic blood pressure (SBP) and diastolic blood pressure (DBP) measurements in adulthood are taken from participants in the Fels Longitudinal Study. Childhood growth curves are estimated separately for stature and BMI using the Preece–Baines and third-degree polynomial models, respectively. Associations between the resulting parameter estimates and adult blood pressure are then examined using linear mixed models. Our findings show that the ages of achievement of the stature-based growth onset and peak velocity, as well as the age of achievement of the BMI-based adiposity rebound, are negatively associated with adult blood pressure, implying that early height or BMI growth can lead to increased blood pressure in adulthood. There were subtle differences in these relationships based on age and gender, and also between SBP and DBP. These results expand on the existing literature, showing that not only childhood body size, but also the timing of childhood growth can have a deleterious effect on adult cardiovascular health.

Ilex paraguariensis (yerba mate) has a beneficial effect in the management of obesity. Here, we studied the effects of yerba mate on hypothalamic changes in leptin and insulin signalling, oxidative stress and liver morphology and metabolism in postnatal early overfeeding (EO) Wistar rats. To induce EO, the litter size was reduced to three pups per dam, and litters with 10 pups per dam were used as a control (10 litters each). On postnatal day (PN) 150, EO offspring were subdivided into EO and EO+mate groups (10 animals each), which were treated with water or mate tea [1 g/kg body weight (BW)/day, by gavage], respectively, for 30 days. The C offspring received water. On PN180, yerba mate treatment prevented BW gain and reduced total body fat, visceral fat and food intake in comparison with the EO group. Leptin and insulin signalling in the hypothalamus measured by Western blotting was reduced only in the EO group. Yerba mate treatment had a greater impact on insulin signalling normalization. In the liver, yerba mate treatment normalized antioxidant enzyme activities and, consequently, decreased lipid peroxidation, determined by malondialdehyde content. In addition, the steatosis level and the liver triglyceride content were also restored. Thus, for the first time, yerba mate was demonstrated to increase antioxidant defences and improve liver metabolism in adult rats that were overfed during lactation, possibly through improvements in the hypothalamic action of insulin. These findings may be important for the treatment of obesity-related disorders.