Mono-2-ethylhexyl phthalate (MEHP) is the primary metabolite of the ubiquitous plasticizer and toxicant, di-2-ethylhexyl phthalate. MEHP exposure has been linked to abnormal development, increased oxidative stress, and metabolic syndrome in vertebrates. Nuclear factor, Erythroid 2 Like 2 (Nrf2), is a transcription factor that regulates gene expression in response to oxidative stress. We investigated the role of Nrf2a in larval steatosis following embryonic exposure to MEHP. Wild-type and nrf2a mutant (m) zebrafish embryos were exposed to 0 or 200 μg/l MEHP from 6 to either 96 (histology) or 120 hours post fertilization (hpf). At 120 hpf, exposures were ceased and fish were maintained in clean conditions until 15 days post fertilization (dpf). At 15 dpf, fish lengths and lipid content were examined, and the expression of genes involved in the antioxidant response and lipid processing was quantified. At 96 hpf, a subset of animals treated with MEHP had vacuolization in the liver. At 15 dpf, deficient Nrf2a signaling attenuated fish length by 7.7%. MEHP exposure increased hepatic steatosis and increased expression of peroxisome proliferator-activated receptor alpha target fabp1a1. Cumulatively, these data indicate that developmental exposure alone to MEHP may increase risk for hepatic steatosis and that Nrf2a does not play a major role in this phenotype.

Nephrogenesis in the rat starts mid-gestation and continues into lactation. Maternal low protein (LP) intake leads to renal injury in rats and associates with mild renal injury in humans. We hypothesized that LP during early nephrogenesis or throughout gestation would induce more renal injury in rat offspring than when LP was only present before nephrogenesis. Pregnant rats were fed LP diet (9% casein) at early gestation (LPE, day 0–7), mid (LPM, day 8–14), late (LPL, day 15–22) or throughout gestation (LPA, day 0–22) and compared to controls on 18% casein diet. Offspring were studied at 18 months. Renal injury was assessed by 24 h proteinuria, plasma urea, antioxidant enzyme activities, and apoptosis (Bax/Bcl2). Proteinuria was higher in LPM males and LPE and LPM females. In LPM males glutathione peroxidase activity was lower, while in LPE males catalase activity was higher. Antioxidants were not much affected in females. Bax expression was higher in LPM males and females, while Bcl2 expression was higher in LPA females. Thus even before nephrogenesis (day 0–7), LP impacted on renal integrity in adult life, while LP during a later phase (day 15–22) or throughout gestation had less effect. In summary, for aging rat kidney LP poses the greatest threat when restricted to early nephrogenesis.

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.

Obesity and its complications occur at alarming rates worldwide. Epidemiological data have associated perinatal conditions, such as malnutrition, with the development of some disorders, such as obesity, dyslipidemia, diabetes, and cardiovascular diseases, in childhood and adulthood. Exclusive breastfeeding has been associated with protection against long-term chronic diseases. However, in humans, the interruption of breastfeeding before the recommended period of 6 months is a common practice and can increase the risk of several metabolic disturbances. Nutritional and environmental changes within a critical window of development, such as pregnancy and breastfeeding, can induce permanent changes in metabolism through epigenetic mechanisms, leading to diseases later in life via a phenomenon known as programming or developmental plasticity. However, little is known regarding the underlying mechanisms by which precocious weaning can result in adipose tissue dysfunction and endocrine profile alterations. Here, the authors give a comprehensive report of the different animal models of early weaning and programming that can result in the development of metabolic syndrome. In rats, for example, pharmacological and nonpharmacological early weaning models are associated with the development of overweight and visceral fat accumulation, leptin and insulin resistance, and neuroendocrine and hepatic changes in adult progeny. Sex-related differences seem to influence this phenotype. Therefore, precocious weaning seems to be obesogenic for offspring. A better understanding of this condition seems essential to reducing the risk for diseases. Additionally, this knowledge can generate new insights into therapeutic strategies for obesity management, improving health outcomes.

Intrauterine growth restriction (IUGR) is associated with adverse perinatal outcomes and late-onset diseases in offspring. Eating disorders, voluntary caloric restriction and maternal undernutrition can all induce IUGR but a relevant model is required to measure all its possible consequences. In this work, pregnant rabbits were used as an IUGR model. Control females (n=4) received ad libitum diet throughout pregnancy, whereas underfed females (n=5) were restricted to 50% of their daily requirements. Offspring size was measured by ultrasonography and in vivo at birth. Hemodynamic features of the umbilical cords and middle cerebral arteries (systolic peak velocity, end diastolic velocity, pulsatility index and resistance index) were characterized by Doppler ultrasonography. At day 21, maternal underfeeding resulted in a significant reduction of fetal size (occipito-nasal length). At birth, the size of kits from the underfed group was significantly lower (lower crown-rump length, biparietal and transversal thoracic diameters) and a reduced weight with respect to the control group. Feed restriction altered blood flow perfusion compared with does fed ad libitum (significant higher systolic peak, time-averaged mean velocities and lower end diastolic velocity). Fetuses affected by IUGR presented with compensative brain-sparing effects when compared with the control group. In conclusion, the present study supports using rabbits and the underfeeding approach as a valuable model for IUGR studies. These results may help to characterize IUGR alterations due to nutrient restriction of mothers in future research.

The development and life performance of 404 high-producing Holstein dairy cows was studied from birth onwards and during two lactations. The management, environment and parental genetics of the cows were known in detail. Cluster analysis identified four performance ‘types’: high-yielding (HY) cows and persistently high-yielding (PHY) cows, which accounted for 33% of the animals; medium-yielding (MY) cows, 41%; and low-yielding (LY) cows, 26%. Prenatal determinants of the life performance of the progeny were analyzed. Developmental and environmental factors were excluded as determinants of performance (including birth weight, level of passive immunity transfer, growth rate, age at first parturition and reproductive efficiency). Life performance did show minor seasonal effects, with more HY cows but less PHY being born during the cold season (90.1% in HY; 58.3% in PHY v. 81.5%). Instead, the single most important factor influencing life performance of daughters was maternal age. HY cows were born from the youngest mothers (1.89±1.14 parturitions, 3.12±1.42-year old), whereas LY cows were born from the oldest (2.72±1.80 parturitions, 3.97±2.01-year old; P<0.001). Life performance of the dams did not differ among clusters. In addition, metabolic parameters (fat and protein yield) were found to correlate significantly with yields between the first and second lactations (milk yield: r=0.357; fat yield: r=0.211; protein yield: r=0.277; P<0.0001), suggesting the influence of the individual. These results suggest that under optimal health, nutritional and environmental conditions, maternal aging is an important determinant of the life performance of progeny and argue for the need to identify conditions that contribute to health and disease in progeny according to the Developmental Origin of Health and Disease or DOHaD concept. Our findings may help the development of novel management guidelines for dairy farms.

Despite many interventions aiming to reduce excessive gestational weight gain (GWG), it is currently unclear the impact on infant anthropometric outcomes. The aim of this review was to evaluate offspring anthropometric outcomes in studies designed to reduce GWG. A systematic search of seven international databases, one clinical trial registry and three Chinese databases was conducted without date limits. Studies were categorised by intervention type: diet, physical activity (PA), lifestyle (diet + PA), other, gestational diabetes mellitus (GDM) (diet, PA, lifestyle, metformin and other). Meta-analyses were reported as weighted mean difference (WMD) for birthweight and birth length, and risk ratio (RR) for small for gestational age (SGA), large for gestational age (LGA), macrosomia and low birth weight (LBW). Collectively, interventions reduced birthweight, risk of macrosomia and LGA by 71 g (WMD: −70.67, 95% CI −101.90 to −39.43, P<0.001), 16% (RR: 0.84, 95% CI 0.73–0.98, P=0.026) and 19% (RR: 0.81, 95% CI 0.69–0.96, P=0.015), respectively. Diet interventions decreased birthweight and LGA by 99 g (WMD −98.80, 95% CI −178.85 to −18.76, P=0.016) and 65% (RR: 0.35, 95% CI 0.17–0.72, P=0.004). PA interventions reduced the risk of macrosomia by 51% (RR: 0.49, 95% CI 0.26–0.92, P=0.036). In women with GDM, diet and lifestyle interventions reduced birthweight by 211 and 296 g, respectively (WMD: −210.93, 95% CI −374.77 to −46.71, P=0.012 and WMD:−295.93, 95% CI −501.76 to −90.10, P=0.005, respectively). Interventions designed to reduce excessive GWG lead to a small reduction in infant birthweight and risk of macrosomia and LGA, without influencing the risk of adverse outcomes including LBW and SGA.

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.

Stunting is a measure of overall nutritional status and is a major public health concern because of its association with child mortality and morbidity and later adult performance. This study examined the effects of pregnancy events, birth characteristics and infant risk exposure on stunting at age 2 years. The study, established in 1990 in Soweto, an urban South African township, included 1098 mother–infant pairs enroled in the Birth to Twenty Plus longitudinal birth cohort study. In total, 22% of children were stunted at age 2 years, with males at greater risk than females [24.8 v. 19.4%, odds ratio (OR)=1.38; 95% confidence interval (CI): 1.03, 1.83]. In unadjusted analysis, male sex, household socio-economic status (SES), overcrowding, maternal age, maternal education, single motherhood, ethnicity, birth weight, gestational age and duration of infant breastfeeding were all significantly associated with stunting. In multivariable analysis, higher birth weight was protective against stunting for both sexes. Higher maternal education was protective for females only (adjusted odds ratio (AOR)=0.35; 95% CI: 0.14, 0.87), whereas wealthier household SES protected males (AOR for richest SES group=0.39; 95% CI: 0.16, 0.92). In this and other similar settings, current stunting prevention efforts focussing on primarily providing targeted proximal interventions, such as food supplements, risk undermining the critical importance of addressing key distal determinants of stunting such as SES and maternal education.

Asthma is a chronic respiratory disease with complex etiology. Adverse childhood experiences (ACEs) have been linked to asthma in adulthood. Underlying potential mechanisms for the ACE-asthma relationship include stress-induced inflammatory pathways and immune dysregulation. We conducted a cross-sectional secondary data analysis of the 2013 Alberta ACE Survey to explore the relationship between latent ACE factors and self-reported adult asthma. We evaluated the underlying correlation structure among eight different ACEs using exploratory factor analysis. We conducted a logistic regression model to evaluate whether ACE factors retained from the factor analysis predicted self-reported asthma in adulthood. Results were reported as odds ratios (ORs) with 95% confidence intervals (CIs). We analyzed ACE survey results from 1207 participants. Factor analysis yielded four ACE latent factors: factor 1/relational violence, factor 2/negative home environment, factor 3/illness at home, and factor 4/sexual abuse. Results of the logistic regression showed that experiencing sexual abuse (OR: 3.23; 95% CI: 1.89, 5.23), relational violence (OR: 1.99; 95% CI: 1.17, 3.38), and being exposed to a negative home environment (OR: 1.86; 95% CI: 1.03, 3.35) were predictive of a diagnosis of asthma in adulthood, whereas living in a household with someone experiencing illness did not show an effect (OR: 1.38; 95% CI: 0.75, 2.56). Factor analysis provides an effectual approach to understand the long-term impact of ACEs on respiratory health. Our findings have important implications to understand the developmental origins of asthma in adulthood and inform interventions aimed at reducing the lasting negative impact of childhood adversities on future respiratory health.

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.

In many human populations, especially those living in regions with pronounced climatic differences between seasons, the most sensitive (prenatal and neonatal) developmental stages occur in contrasting conditions depending on the season of conception. The difference in prenatal and postnatal environments may be a factor significantly affecting human development and risk for later life chronic diseases. Factors potentially contributing to this kind of developmental programming include nutrition, outdoor temperature, infectious exposures, duration of sunlight, vitamin D synthesis, etc. Month of birth is commonly used as a proxy for exposures which vary seasonally around the perinatal period. Season-of-birth patterns have been identified for many chronic health outcomes. In this review, the research evidence for the seasonality of birth in adult-life disorders is provided and potential mechanisms underlying the phenomenon of early life seasonal programming of chronic disease and longevity are discussed.

In rats, maternal exposure to restraint stress during pregnancy can induce abnormalities in the cardiovascular and central nervous systems of the offspring. These effects are mediated by long-lasting hyperactivation of the hypothalamic–pituitary–adrenal axis. However, little is known about the potential effects of stress during pregnancy on metabolic systems. We examined the effect of restraint stress in pregnant mice on the liver function of their offspring. The offspring of stressed mothers showed significantly higher lipid accumulation in the liver after weaning than did the controls; this accumulation was associated with increased expression of lipid metabolism-related proteins such as alanine aminotransferase 2 diglyceride acyltransferase 1, peroxisome proliferator-activated receptor gamma and glucocorticoid receptor. Additionally, we observed increased levels of 11β-hydroxysteroid dehydrogenase type 1, an intercellular mediator that converts glucocorticoid from the inactive to the active form, in the foetal and postnatal periods. These results indicate that restraint stress in pregnancy in mice induces metabolic abnormalities via 11β-hydroxysteroid dehydrogenase type 1-related pathways in the foetal liver. It is therefore possible that exposure to stress in pregnant women may be a risk factor for metabolic syndromes (e.g. fatty liver) in children.

Caesarean delivery has been linked to a number of inflammatory conditions in childhood and adolescence. Yet the mechanisms underlying these associations and their generalizability across contexts with different postnatal feeding and pathogenic exposures remain unclear. This study tests the association between delivery type and three measures of immune function, inflammation, morbidity and leukocyte proportions, in Ecuadorian infants and children aged 6 months to 2 years. Data were collected from mother–child pairs participating in a nationally representative health and nutrition survey Encuesta Nacional de Salud y Nutricion (ENSANUT-ECU) conducted in 2012. The analytic sample includes 828 mothers and infants with delivery information and measured biomarkers. Poisson regression models were used to examine the association between delivery type and markers of immune function, controlling for maternal and infant characteristics, including age, sex, sociodemographic characteristics and medical indications. 40.8% (n=338) of sample infants and children were delivered by caesarean. Compared to those born vaginally, infants born by caesarean were less likely to have elevated C-reactive protein (CRP) [CRP>2 mg/l; risk ratio (RR): 0.76, 95% confidence interval (CI): 0.58–1.00] and more likely to have illness symptoms (RR: 1.22, 95% CI: 1.01–1.46) and elevated basophils (RR: 1.83, 95% CI: 1.03–3.25). No other immune cell proportions differed by delivery type. The results suggest that differences in the perinatal exposures accompanying caesarean delivery may alter immune development and function, particularly in the inflammatory response to infection and in cells involved in the allergic response, across infancy and early childhood. Understanding the pathways linking perinatal exposures to immune development is important for preventing the development of inflammatory conditions.

Low birth weight and a rapid weight gain in early childhood may lead to an increased risk for developing cardiovascular disease later in life, such as hypertension and dyslipidaemia. In this study, we examined the associations between size at birth, relative weight gain in infancy and childhood with specific cardiovascular disease risk factors in early adulthood. Adolescents (n=1935) from the Birth to Twenty plus (BT20+) cohort were included in the analysis. The following were treated as exposure variables: weight at birth, and relative conditional weight gain (CW), independent of height, between ages 0–24 months and 24–48 months. Outcomes were serum lipids and body composition variables at age 18 years. After adjusting for sex and other confounders, early life exposures were not associated with adolescent lipid profile. Following adjustment for sex and height (body size), birth weight [β=0.704 (0.40, 1.01)], CW 0–24 [β=1.918 (1.56, 2.28)] and CW24–48 [β=1.485 (1.14, 1.82)] accounted for 48% of the variance in fat mass. However, birth weight [β=0.773 (0.54, 1.01)], CW 0–24 [β=1.523 (1.24, 1.80)] and CW24–48 [β=1.226 (0.97, 1.49)] were also positively predicted and accounted for 71% of the variance in fat mass in adolescence (P<0.05). Our data suggests that birth weight and weight gain during infancy and early childhood independent of linear growth are related to adolescent body composition but not blood lipid profiles in an urban African population.

Rates of chronic kidney disease (CKD) among Indigenous groups in Australia exceed non-Indigenous rates eight-fold. Using kidney volume as a surrogate for nephron number, we carried out a study to determine if Indigenous neonates have a smaller kidney volume (and thus a reduced nephron number) from birth compared with non-Indigenous neonates. We recruited term and preterm neonates (<32 weeks) at a tertiary care neonatal unit over a 12 months period. Preterm neonates were assessed (renal sonography and renal function measurement) at 32 weeks corrected age (CA) and again at 38 weeks CA when blood pressure was also measured. All term neonates were assessed in the first post-natal week, including renal sonography, renal function and blood pressure measurement. The primary outcome measured was total kidney volume (TKV) and estimated glomerular filtration rate (eGFR) was a secondary outcome. Data was available for 44 preterm (11 Indigenous) and 39 term (13 Indigenous) neonates. TKV of Indigenous neonates was significantly lower at 32 weeks [12.0 (2.0) v. 15.4 (5.1) ml; P=0.03] and 38 weeks CA [18.6 (4.0) v. 22.6 (5.9) ml; P=0.04] respectively. Term Indigenous neonates also had smaller kidney volumes compared with non-Indigenous neonates. Despite a smaller kidney volume (and reduced nephron number), Indigenous neonates did not have a significantly lower eGFR. Indigenous neonates achieve similar eGFRs to Non-Indigenous neonates, presumably through a higher single nephron filtration rate. This places Indigenous neonates at a greater risk of long-term kidney damage later in life.

We have previously shown that neonatal high oxygen (O2) exposure in rats leads to hypertension and vascular dysfunction in adulthood. Pulse-wave velocity (PWV), an indirect measure of vascular biophysical properties (arterial stiffness or distensibility), is a sensitive marker of cardiovascular health. Its measurement in rats is mostly based on invasive hemodynamics measurements, prohibiting longitudinal studies particularly relevant in models of developmental programming of cardiovascular dysfunctions. With this study, we sought (1) to verify the feasibility and validity of measuring of aortic PWV in Sprague–Dawley rats by ultrasound; (2) to use the technique to compare aortic PWV in adult rats exposed to O2 as newborns (80% day 3–10 of life) v. controls; and (3) to develop an algorithm to calculate PWV in a non-invasive manner. We calculated aortic PWV using standard echocardiography and electrocardiogram, and validated the measures with PWV obtained by intraaortic catheters. Aortic full length was measured at sacrifice. PWV was significantly increased in O2 exposed (505 ± 18 cm/s) v. control animals (421 ± 17 cm/s, P < 0.01). With regard to weight, femur length and distance from the manubrium to the anal margin (MA length), the latter showed the best correlation (R = 0.84, P < 0.0001) with full aorta length derived from (L) = 0.339 × (MA length) + 4.281. The current data using echo-Doppler method demonstrated increased aortic stiffness in adult rats exposed to hyperoxia as newborns and suggests that non-invasive longitudinal studies of aortic PWV can be performed using the proposed algorithm for estimation of the full aorta length.

Recently, large-scale trials of behavioural interventions have failed to show improvements in pregnancy outcomes. They have, however, shown that lifestyle support improves maternal diet and physical activity during pregnancy, and can reduce weight gain. This suggests that pregnancy, and possibly the whole periconceptional period, represents a ‘teachable moment’ for changes in diet and lifestyle, an idea that was made much of in the recent report of the Chief Medical Officer for England. The greatest challenge with all trials of diet and lifestyle interventions is to engage people and to sustain this engagement. With this in mind, we propose a design of intervention that aims simultaneously to engage women through motivational conversations and to offer access to a digital platform that provides structured support for diet and lifestyle change. This intervention design therefore makes best use of learning from the trials described above and from recent advances in digital intervention design.

Chorioamnionitis and intrauterine growth retardation (IUGR) are risk factors for cerebral palsy (CP). Common bacteria isolated in chorioamnionitis include group B Streptococcus (GBS) serotypes Ia and III. Little is known about the impact of placental inflammation induced by different bacteria, including different GBS strains. We aimed to test the impact of chorioamnionitis induced by two common GBS serotypes (GBSIa and GBSIII) on growth and neuromotor outcomes in the progeny. Dams were exposed at the end of gestation to either saline, inactivated GBSIa or GBSIII. Inactivated GBS bacteria invaded placentas and triggered a chorioamnionitis featured by massive polymorphonuclear cell infiltrations. Offspring exposed to GBSIII – but not to GBSIa – developed IUGR, persisting beyond adolescent age. Male rats in utero exposed to GBSIII traveled a lower distance in the Open Field test, which was correlating with their level of IUGR. GBSIII-exposed rats presented decreased startle responses to acoustic stimuli beyond adolescent age. GBS-exposed rats displayed a dysmyelinated white matter in the corpus callosum adjacent to thinner primary motor cortices. A decreased density of microglial cells was detected in the mature corpus callosum of GBSIII-exposed males – but not females – which was correlating positively with the primary motor cortex thickness. Altogether, our results demonstrate a causal link between pathogen-induced acute chorioamnionitis and (1) IUGR, (2) serotype- and sex-specific neuromotor impairments and (3) abnormal development of primary motor cortices, dysmyelinated white matter and decreased density of microglial cells.

Intrauterine growth restriction (IUGR) and fetal exposure to a maternal high-fat diet (HFD) independently increase the risk of developing obesity in adulthood. Excess glucocorticoids increase obesity. We hypothesized that surgically induced IUGR combined with an HFD would increase adiposity and glucocorticoids more than in non-IUGR offspring combined with the same HFD, findings that would persist despite weaning to a regular diet. Non-IUGR (N) and IUGR (I) rat offspring from dams fed either regular rat chow (R) or an HFD (H) were weaned to either a regular rat chow or an HFD. For non-IUGR and IUGR rats, this study design resulted in three diet groups: offspring from dams fed a regular diet and weaned to a regular diet (NRR and IRR), offspring rats from dams fed an HFD and weaned to a regular diet (NHR and IHR) and offspring from dams fed an HFD and weaned to an HFD (NHH and IHH). Magnetic resonance imaging or fasting visceral and subcutaneous adipose tissue collection occurred at postnatal day 60. IHH male rats had greater adiposity than NHH males, findings that were only partly normalized by weaning to a regular chow. IHH male rats had a 10-fold increase in serum corticosterone levels. IHH female rats had increased adiposity and serum triglycerides. We conclude that IUGR combined with an HFD throughout life increased adiposity, glucocorticoids and triglycerides in a sex-specific manner. Our data suggest that one mechanism through which the perinatal environment programs increased adiposity in IHH male rats may be via increased systemic glucocorticoids.