Early supplementation with oregano essential oil (EO) in milk replacer (MR) may improve growth, immune responses, the microbiota and the metabolome in dairy calves during pre-weaning and in adulthood. Sixteen female dairy calves (3 days of age) were divided in two groups (n = 8/group): the control group (no EO) and the EO group (0.23 ml of EO in MR during 45 days). After weaning, calves were kept in a feedlot and fed ad libitum. The animals were weighed, and blood and faecal samples were collected on days 3 (T0), 45 (T1) and 370 (T2) to measure the biochemical profile and characterise peripheral blood mononuclear cells (PBMCs; CD4+, CD8+, CD14+, CD21+ and WC1+), the metabolome and microbiota composition. The EO group only had greater average daily weight gain during the suckling (EO supplementation) period (P = 0.030). The EO group showed higher average CD14+ population (monocytes) values, a lower abundance of Ruminococcaceae UCG-014, Faecalibacterium, Blautia and Alloprevotella and increased abundances of Allistipes and Akkermansia. The modification of some metabolites in plasma, such as butyric acid, 3-indole-propionic acid and succinic acid, particularly at T1, are consistent with intestinal microbiota changes. The data suggest that early EO supplementation increases feed efficiency only during the suckling period with notable changes in the microbiota and plasma metabolome; however, not all of these changes can be considered desirable from a gut health point of view. Additional research studies is required to demonstrate that EOs are a viable natural alternative to antibiotics for improving calf growth performance and health.

Offspring generated by in vitro fertilization (IVF) are believed to be healthy but display a possible predisposition to chronic diseases, like hypertension and glucose intolerance. Since epigenetic changes are believed to underlie such phenotype, this study aimed at describing global DNA methylation changes in the liver of adult mice generated by natural mating (FB group) or by IVF. Embryos were generated by IVF or natural mating. At 30 weeks of age, mice were sacrificed. The liver was removed, and global DNA methylation was assessed using whole-genome bisulfite sequencing (WGBS). Genomic Regions for Enrichment Analysis Tool (GREAT) and G:Profilerβ were used to identify differentially methylated regions (DMRs) and for functional enrichment analysis. Overrepresented gene ontology terms were summarized with REVIGO, while canonical pathways (CPs) were identified with Ingenuity® Pathway Analysis. Overall, 2692 DMRs (4.91%) were different between the groups. The majority of DMRs (84.92%) were hypomethylated in the IVF group. Surprisingly, only 0.16% of CpG islands were differentially methylated and only a few DMRs were located on known gene promoters (n = 283) or enhancers (n = 190). Notably, the long-interspersed element (LINE), short-interspersed element (SINE), and long terminal repeat (LTR1) transposable elements showed reduced methylation (P < 0.05) in IVF livers. Cellular metabolic process, hepatic fibrosis, and insulin receptor signaling were some of the principal biological processes and CPs modified by IVF. In summary, IVF modifies the DNA methylation signature in the adult liver, resulting in hypomethylation of genes involved in metabolism and gene transcription regulation. These findings may shed light on the mechanisms underlying the developmental origin of health and disease.

The development of the fetal movement acceleration measurement (FMAM) recorder has enabled the accurate counting of gross fetal movements. The aim of the study was to investigate whether gross fetal movement is related to a newborn’s size. A total of 90 pregnant women who delivered singleton infant at term were recruited. Gross fetal movements were counted using an FMAM recorder during maternal sleep. The ratio of movement positive 10-s epochs to all epochs during one night was calculated as an index of fetal movement. Independent explanatory variables for the fetal movement index were selected from eight possibilities, that is, maternal age, gestational week, and the six physical measures of the newborn (height, weight, head circumference, chest circumference, Kaup index, and the ratio of head to chest circumference) with the stepwise regression procedure. The selected physical variables and the fetal movement index were analyzed using multiple regression analysis. A total of 2812.95 h from 423 night records were available. Gestational weeks and weight of the newborn were selected as the significant independent variables. Multiple regression analysis revealed that newborn weight had a positive correlation with the fetal movement index (p < 0.0001). The multiple regression equation was “The fetal movement index (%) = 34.9989−0.9088 × gestational weeks + 0.0033 × newborn weight (g).” A person’s physical ability and lifetime activity level may originate from fetal health. This study may provide a new way of looking at the Developmental Origins of Health and Disease theory.

Prenatal insults during fetal development result in increased likelihood of developing chronic disease. Obesity, the biggest risk factor for the development of metabolic disease, is affected by several genetic and environmental factors. High-fat diet (HFD) consumption is usually linked with the development of obesity. The main goal of this study was to analyze the impact of the exposure to a HFD in prenatally stressed animals. For this purpose, we subjected pregnant BALB/c mice to restraint stress for 2 h a day between gestational day (GD) 14 and GD 21. Prenatally stressed and control offspring of both sexes were postnatally exposed to a HFD for 24 weeks. We found that prenatal stress (PS) per se produced disturbances in males such as increased total blood cholesterol and triglycerides, with a decrease in mRNA expression of sirtuin-1. When these animals were fed a HFD, we observed a rise in glucose and insulin levels and an increase in visceral adipose tissue gene expression of leptin, resistin, and interleukin-1 beta. Although females proved to be more resilient to PS consequences, when they were fed a HFD, they showed significant metabolic impairment. In addition to the changes observed in males, females also presented an increase in body weight and adiposity and a rise in cholesterol levels.

Considering the negative effects of glucocorticoid treatment, especially during fetal development it is important to investigate effectors decreasing such disadvantages. The aim of this study was to investigate the effect of prenatally administered dexamethasone (Dex), a synthetic glucocorticoid, on the histomorphometry of the femur in the offspring of spiny mice. The study was performed on 24 pregnant spiny mice. The time of the experiment included the prenatal period between the 20th day of gestation until birth (pregnancy lasts on average of 36–38 days). The mice from the experimental group received dexamethasone per os in a dose of 125 mg/kg birth weight daily. At the end, the newborns from the experimental and control group were weighted and euthanized. Maternal Dex treatment resulted in a 17% decrease in birth weight in newborns. Dex administration significantly reduced the thickness of the hypertrophy zone of the growth plate by 34% and total thickness by 8,7%. In addition, Dex decreased the number of cells in the articular cartilage by 27% and significantly decreased their diameter by 5%. Dex also affected the structure and spatial distribution of thick and thin collagen fibers, lowering the proportion of thin fibers compared with the control group. Moreover, Dex treatment considerably lowered the amount of proteoglycans in articular and growth cartilages. Exposure to glucocorticoids in pregnant spiny mice affects cartilage development by accelerating maturity of collagen fibers and growth plate, presumably along with further disruption of longitudinal growth of long bones.

Exposure to environmental chemicals and other environmental stressors have health impacts on the fetus that may not be apparent until later in life. The concept of developmental origins of disease should be expanded to include these early life exposures in addition to the effects of nutrition and maternal factors. This paper will describe the toxicological, biological and epidemiological issues that are pertinent to conducting research on environmental exposures early in life and their health consequences over the life span.

The aim of our article was to review the current literature on the effects of metabolic (re) programming on childhood obesity. PubMed/MEDLINE was the data source used to track the studies. Descriptors applied: children obesity, epigenetic, metabolic programming, exercise and nutrition. The focus was to analyze and discuss the international findings on the theme. The gathering of the papers was performed between June and August 2014. The search of articles with the descriptors used found 33.054 studies. In all, 5.709 studies were selected by crossing chosen keywords. Among these, after careful reading of the titles, 712 papers were considered potential as references. After applying inclusion/exclusion criteria, 50 studies were selected from 132 eligible abstracts. Most studies linked the development and treatment of obesity from epigenetically stimulated metabolic programming during the early stages of pregnancy and life. This review provides theoretical basis to the understanding that the programmed development of childhood obesity may be linked to early exposure to environmental factors, such as (nutrition and regular practice of exercise) and stimulus can epigenetically alter the modulation of the obesogenic metabolic behavior during pregnancy and the developmental stages of children and/or postpone the pathophysiologic disease stage to adulthood.

Early life stress has been shown to contribute to alterations in biobehavioral regulation. Whereas many different forms of childhood adversities have been studied in relation to cardiovascular outcomes, very little is known about potential associations between caregivers’ verbally aggressive behavior and heart rate and blood pressure in the child. This prospective study examined whether maternal verbally aggressive behavior in early infancy is associated with heart rate or blood pressure at age 5–6. In the Amsterdam Born Children and their Development study, a large prospective, population-based birth cohort, maternal verbally aggressive behavior was assessed by questionnaire in the 13th week after birth. The child’s blood pressure and heart rate were measured during rest at age 5–6 (n=2553 included). Maternal verbally aggressive behavior in infancy was associated with a higher systolic blood pressure (SBP) both in supine and sitting position after adjustment for sex, height and age (SBP supine B=1.01 mmHg; 95% CI [0.06; 1.95] and SPB sitting B=1.29 mmHg; 95% CI [0.12; 2.46]). Adjustment for potential confounding variables, such as other mother–infant dyad aspects, family hypertension and child’s BMI, only slightly attenuated the associations (SBP supine B=0.99 mmHg; 95% CI [0.06; 1.93] and SPB sitting B=1.11 mmHg; 95% CI [−0.06; 2.27]). Maternal verbally aggressive behavior was not associated with diastolic blood pressure or heart rate at age 5–6. Maternal verbally aggressive behavior might be an important early life stressor with negative impact on blood pressure later in life, which should be further investigated. Possible underlying mechanisms are discussed.

Unbalanced nutrition during critical windows of development is implicated in determining the susceptibility to hypertension and cardiovascular disease in adult life, but the underlying mechanisms during fetal life have not been fully elucidated. We investigated the effects of moderate nutritional restriction during critical windows in gestation on late gestation fetal sheep growth, cardiovascular and renal renin-angiotensin system function. Ewes were fed 100% nutrient requirements (control), or 40–50% nutrient requirements during the peri-implantation period (1–31 days gestation (dGA), PI40 and PI50), or 50% nutrient requirements in late gestation (104–127 dGA). At 125 ± 2 dGA, fetal cardiovascular and renal function were measured at baseline, and during frusemide, angiotensin II (Ang II), phenylephrine and hypoxia challenges. Maternal undernutrition had no effect on fetal biometry, kidney weight, nephron number, basal cardiovascular function or cardiovascular and renal responses to frusemide. Fetal blood pressure response to Ang II was blunted in PI50 (P < 0.05), but not in PI40 groups. There was no difference between groups in the cardiovascular or endocrine response to hypoxia. The lack of effect of moderate undernutrition within key developmental windows of fetal kidney development on fetal renal structure and function suggests that renal mechanisms do not underlie our previous observations of cardiovascular dysfunction in adulthood following early-life undernutrition.

The availability of clinically feasible infant body composition assessment can inform current questions regarding the developmental origins of chronic disease. A strategic approach will facilitate more rapid advancement in knowledge. The objective of this study was to summarize published evidence and ongoing research activity in infant body composition using the PEA POD® infant body composition system. All published studies using the PEA POD® were identified and grouped according to study population and question. All centers with PEA POD® units were invited to participate in an online survey regarding past, current and future PEA POD® use, and results were analyzed using descriptive statistics. The resulting information was used to identify gaps or limitations in existing knowledge, thus highlighting potential research priorities. Twenty-seven published articles were identified and grouped into six research themes. Although the number of infants studied is significant in some areas, interpretation of data is limited by methodological differences. Survey responses were received from 16 of ∼60 centers. Research themes echoed those identified from the published literature. Controlling for or reporting potential confounding variables is essential for understanding infant body composition data. Measurement of health outcome variables would be helpful in identifying associations.

The content of omega-3 long-chain polyunsaturated fatty acids (n−3 LCPUFA) in chicken meat can be boosted by feeding broilers a diet containing α-linolenic acid (ALA, from flaxseed oil), some of which is converted by hepatic enzymes to n−3 LCPUFA. However, most of the accumulated n−3 polyunsaturated fatty acid (PUFA) in meat tissues is still in the form of ALA. Despite this, the levels of chicken diets are being enhanced by the inclusion of vegetable and marine sources of omega-3 fats. This study investigated whether the capacity of chicken for n−3 LCPUFA accumulation could be enhanced or inhibited by exposure to an increased supply of ALA or n−3 LCPUFA in ovo. Breeder hens were fed either flaxseed oil (High-ALA), fish oil (high n−3 LCPUFA) or tallow- (low n−3 PUFA, Control) based diets. The newly hatched chicks in each group were fed either the High-ALA or the Control diets until harvest at 42 days’ post-hatch. The n−3 PUFA content of egg yolk and day-old chick meat closely matched the n−3 PUFA composition of the maternal diet. In contrast, the n−3 PUFA composition of breast and leg meat tissues of the 42-day-old offspring closely matched the diet fed post-hatch, with no significant effect of maternal diet. Indeed, there was an inhibition of n−3 LCPUFA accumulation in meat of the broilers from the maternal Fish-Oil diet group when fed the post-hatch High-ALA diet. Therefore, this approach is not valid to elevate n-3 LCPUFA in chicken meat.

Several studies have reported association of altered levels of lipids and some trace elements with risk factors for cardiovascular disease development in adulthood. Accordingly, the present study aimed to determine the relationship among the serum levels of copper (Cu), zinc (Zn), lipids, lipoproteins and apolipoproteins in preterm infants through an assessment of atherogenic indices shortly after birth. Blood samples were collected within 20 min of birth from 45 preterm infants with gestational ages ranging from 32 to 35 weeks. Serum Cu, Zn, total cholesterol (TC), low-density lipoprotein cholesterol (LDLc), high-density lipoprotein cholesterol (HDLc), apolipoprotein-A1 (apoA1) and apolipoprotein-B (apoB) levels were measured, and the TC/HDLc, LDLc/HDLc and apoB/apoA1 ratios were calculated. Upon determining the correlation between the levels of Cu, Zn and these indices of lipid metabolism, triglyceride (TG) and Cu were found to correlate negatively with birth weight (BW) and the standard deviation (s.d.) score for body weight. Furthermore, Cu levels correlated positively with the TG level and TC/HDLc, LDLc/HDLc and apoB/apoA1 ratios and negatively with the HDLc level and HDLc/apoA1 ratios. However, a stepwise multiple regression analysis indicated that the s.d. score for BW and TG level were significant independent determinants of the Cu level. In contrast, Zn did not correlate with any of these indices. In conclusion, intrauterine growth restriction and the TG level at birth influence Cu levels in preterm infants, whereas atherogenic indices do not affect this parameter.

Impaired β-cell development and insulin secretion are characteristic of intrauterine growth-restricted (IUGR) fetuses. In normally grown late gestation fetal sheep pancreatic β-cell numbers and insulin secretion are increased by 7–10 days of pulsatile hyperglycemia (PHG). Our objective was to determine if IUGR fetal sheep β-cell numbers and insulin secretion could also be increased by PHG or if IUGR fetal β-cells do not have the capacity to respond to PHG. Following chronic placental insufficiency producing IUGR in twin gestation pregnancies (n=7), fetuses were administered a PHG infusion, consisting of 60 min, high rate, pulsed infusions of dextrose three times a day with an additional continuous, low-rate infusion of dextrose to prevent a decrease in glucose concentrations between the pulses or a control saline infusion. PHG fetuses were compared with their twin IUGR fetus, which received a saline infusion for 7 days. The pulsed glucose infusion increased fetal arterial glucose concentrations an average of 83% during the infusion. Following the 7-day infusion, a square-wave fetal hyperglycemic clamp was performed in both groups to measure insulin secretion. The rate of increase in fetal insulin concentrations during the first 20 min of a square-wave hyperglycemic clamp was 44% faster in the PHG fetuses compared with saline fetuses (P<0.05). There were no differences in islet size, the insulin+ area of the pancreas and of the islets, and β-cell mass between groups (P>0.23). Chronic PHG increases early phase insulin secretion in response to acute hyperglycemia, indicating that IUGR fetal β-cells are functionally responsive to chronic PHG.

Risk factors associated with intrauterine growth restriction (IUGR) have previously been identified, but few studies have described the relationship between IUGR and maternal stress caused by exposure to civil unrest. Here, we investigate this relationship during the Mount Elgon crisis in western Kenya between 2006 and 2008, following a period of violence. Birth weight data were compared between three hospitals in an exposed area, Mount Elgon (n=570), and one hospital in a control area, Kimilili (n=530). In a sub-analysis, the most stress exposed hospital, Bungoma West (n=211), was compared with the control hospital in Kimilili. Adjustments were made for offspring sex, gestational age and parity. The difference in mean birth weight between the most stress-exposed hospital (Bungoma West) and the control hospital (Kimilili) was 91 g after full adjustment (P=0.041). In conclusion, epidemiological data suggest a significant relationship between exposure to civil unrest and IUGR causing lower birth weight.

Early development, throughout gestation and lactation, represents a period of extreme vulnerability during which susceptibility to later metabolic and cardiovascular injuries increases. Maternal diet is a major determinant of the foetal and newborn developmental environment; maternal undernutrition may result in adaptive responses leading to structural and molecular alterations in various organs and tissues, such as the brain and kidney. New nephron anlages appear in the renal cortex up to postnatal day 4 and the last anlages to be formed develop into functional nephrons by postnatal day 10 in rodents. We used a model of undernutrition in rat dams that were food-restricted during the first half of the lactation period in order to study the long-term effects of maternal diet on renal development, behaviour and neural hydromineral control mechanisms. The study showed that after 40% food restriction in maternal dietary intake, the dipsogenic responses for both water and salt intake were not altered; Fos expression in brain areas investigated involved in hydromineral homeostasis control was always higher in the offspring in response to isoproterenol. This was accompanied by normal plasma osmolality changes and typical renal histology. These results suggest that the mechanisms for the control of hydromineral balance were unaffected in the offspring of these 40% food-restricted mothers. Undernutrition of the pups may not be as drastic as suggested by dams’ restriction.

The risk for many chronic diseases appears to be mediated in part by birth weight. Among Aboriginal Canadians, the prevalence of end-stage renal disease and cardiovascular disease risk is disproportionately high, largely because of elevated diabetes prevalence. The relationships between birth weight (and other potential risk factors) and diabetes, hypertension, proteinuria and overweight/obesity were explored in 1439 rural Albertans (Canada), of whom 67.3% were Aboriginal. At voluntary outreach screening programs, demographic and clinical data were measured and recalled birth weights recorded. Statistical modeling using logistic regression was used to evaluate the relationships. In the final adjusted models, associations remained for low birth weight and proteinuria [odds ratio (OR) 2.36; 95% CI 1.24–4.49], as well as for high birth weight and overweight/obesity (OR 1.58; 95% CI 1.00–2.53). These findings emphasize the need to strive for healthy pregnancies, with appropriate weight gains in these and other disadvantaged populations around the world.

We sought to examine whether rat maternal food restriction (MFR) affects the expression of steroidogenesis-related genes Cyp19, Cyp17a1, Insl3 and Gdf-9 in the ovaries of offspring from the first (FRG1) and second (FRG2) generations at pre-pubertal age (week 4) and during adulthood (week 8). At week 4, MFR significantly increased the expression of RNAs for all analyzed genes in both FRG1 and FRG2 females, which may indicate that MFR affects the onset of the reproductive lifespan, by inducing early pubertal onset. At week 8, the Cyp19 gene was still upregulated in MRF-subjected animals (Cyp19: P=0.0049 and P=0.0508 in FRG1 and FRG2, respectively), but MFR induced a significant decrease in Cyp17 and Gdf-9 gene expression in the offspring of both FRG1 and FRG2 females when compared with the controls (Cyp17: P=0.0018 and P=0.0016, respectively; Gdf-9: P=0.0047 and P=0.0023, respectively). This suggests that females at week 8, which should normally be in their optimal reproductive capacity, experience premature ovarian aging. At week 4, the activation of Cyp19 and Cyp17 was higher in the FRG1 ovaries than in the FRG2 ovaries, whereas the extent of Insl3 and Gdf-9 activation was lower in the FRG1 ovaries. This may indicate that FRG2 females were more vulnerable to MFR than their mothers (FRG1) and grandmothers, which is consistent with the ‘predictive adaptive response’ hypothesis. Our findings reveal that MFR may induce intergenerational ovarian changes as an adaptive response to ensure reproductive success before death.

Markers of metabolic abnormalities are commonly found in rodents fed a fructose-rich diet. The purpose of this study was to determine whether the administration of a short-term standard diet to rats is able to improve the lipid profile altered by a fructose-rich diet. The male pups, immediately after birth, were divided in three groups according to the diet for 90 days. Standard diet: a standard diet for the whole experimental period; fructose (60% fructose-rich diet): fructose-rich diet during the entire experimental period; fructose/standard (FS): fructose-rich diet from the neonatal period up to 60 days of age and standard diet from 60 to 90 days of age. A fructose-rich diet from the neonatal period to 60 days reduced weight gain (P<0.05), as well as the weight of adipose tissues in all the regions analyzed (epididymal, mesenteric, retroperitoneal and posterior subcutaneous), and it altered the lipid profile (elevation of triglycerides, total cholesterol, low density lipoprotein (LDL) cholesterol and very low density lipoprotein (VLDL) cholesterol; P<0.05). When a standard diet was administered after the fructose-rich diet, it was able to partially reverse changes to the lipid profile, as total cholesterol levels were significantly different in all the groups (P<0.05), and triglyceride and VLDL cholesterol levels were similar between the control and FS group. In summary, a fructose-rich diet altered the lipid profile, and a standard diet can partially reverse the changed parameters in short term.

Maternal supraphysiological estradiol (E2) environment during pregnancy leads to adverse perinatal outcomes. However, the influence of oocyte exposure to high E2 levels on perinatal outcomes remains unknown. Thus, a retrospective cohort study was conducted to explore the effect of high E2 level induced by controlled ovarian stimulation (COH) on further outcomes after frozen embryo transfer (FET). The study included all FET cycles (n = 10,581) between 2014 and 2017. All cycles were categorized into three groups according to the E2 level on the day of the human Chorionic Gonadotropin trigger. Odds ratios (ORs) and their confidence intervals (CIs) were calculated to evaluate the association between E2 level during COH and pregnancy outcomes and subsequent neonatal outcomes. From our findings, higher E2 level was associated with lower percentage of chemical pregnancy, clinical pregnancy, ongoing pregnancy, and live birth as well as increased frequency of early miscarriage. Preterm births were more common among singletons in women with higher E2 level during COH (aOR1 = 1.93, 95% CI: 1.22–3.06; aOR2 = 2.05, 95% CI: 1.33–3.06). Incidence of small for gestational age (SGA) was more common in both singletons (aOR1 = 2.01, 95% CI: 1.30–3.11; aOR2 = 2.51, 95% CI: 1.69–3.74) and multiples (aOR1 = 1.58, 95% CI: 1.03–2.45; aOR2 = 1.99, 95% CI: 1.05–3.84) among women with relatively higher E2 level. No association was found between high E2 level during COH and the percentage of macrosomia or large for gestational age. In summary, oocyte exposure to high E2 level during COH should be brought to our attention, since the pregnancy rate decreasing and the risk of preterm birth and SGA increasing following FET.