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Advanced age at conception usually refers to human mothers aged 35 years plus and fathers aged 40 years plus. Advanced parental age may be responsible for genetic and/or epigenetic alterations and may affect the health of offspring. Limited epidemiological and experimental studies have addressed the effect of advanced parental age on cardio‐metabolic functions in human and rodent offspring. This mini review aimed to present the knowledge by focusing on adverse and favourable outcomes related to sex‐specific risks and intergenerational inheritance. The outcomes identified by this review were mainly negative, but there were also some positive results. [ABSTRACT FROM AUTHOR]

In humans and animal models, Cesarean section (C‐section) has been associated with alterations in the taxonomic structure of the gut microbiome. These changes in microbiota populations are hypothesized to impact immune, metabolic, and behavioral/neurologic systems and others. It is not clear if birth mode inherently changes the microbiome, or if C‐section effects are context‐specific and involve interactions with environmental and other factors. To address this and control for potential confounders, cecal microbiota from ~3 week old mice born by C‐section (n = 16) versus natural birth (n = 23) were compared under matched conditions for housing, cross‐fostering, diet, sex, and genetic strain. A total of 601 unique species were detected across all samples. Alpha diversity richness (i.e., how many species within sample; Chao1) and evenness/dominance (i.e., Shannon, Simpson, Inverse Simpson) metrics revealed no significant differences by birth mode. Beta diversity (i.e., differences between samples), as estimated with Bray‐Curtis dissimilarities and Aitchison distances (using log[x + 1]‐transformed counts), was also not significantly different (Permutational Multivariate ANOVA [PERMANOVA]). Only the abundance of Lachnoclostridium [Clostridium] scindens was found to differ using a combination of statistical methods (ALDEx2, DESeq2), being significantly higher in C‐section mice. This microbe has been implicated in secondary bile acid production and regulation of glucocorticoid metabolism to androgens. From our results and the extant literature we conclude that C‐section does not inherently lead to large‐scale shifts in gut microbiota populations, but birth mode could modulate select bacteria in a context‐specific manner: For example, involving factors associated with pre‐, peri‐, and postpartum environments, diet or host genetics. [ABSTRACT FROM AUTHOR]

([4]) is that, to combat this effect, they have sought to independently investigate the effect of paternal low protein diet on the sperm alone, on the seminal plasma alone or both sperm and plasma together. Dietary protein restriction of pregnant rats in the F0 generation induces altered methylation of hepatic gene promoters in the adult male offspring in the F1 and F2 generations. Paternal diet impairs F1 and F2 offspring vascular function through sperm and seminal plasma specific mechanisms in mice. [Extracted from the article]

Maternal obesity is a global problem that increases the risk of short‐ and long‐term adverse outcomes for mother and child, many of which are linked to gestational diabetes mellitus. Effective treatments are essential to prevent the transmission of poor metabolic health from mother to child. Metformin is an effective glucose lowering drug commonly used to treat gestational diabetes mellitus; however, its wider effects on maternal and fetal health are poorly explored. In this study we used a mouse (C57Bl6/J) model of diet‐induced (high sugar/high fat) maternal obesity to explore the impact of metformin on maternal and feto‐placental health. Metformin (300 mg kg−1 day−1) was given to obese females via the diet and was shown to achieve clinically relevant concentrations in maternal serum (1669 ± 568 nM in late pregnancy). Obese dams developed glucose intolerance during pregnancy and had reduced uterine artery compliance. Metformin treatment of obese dams improved maternal glucose tolerance, reduced maternal fat mass and restored uterine artery function. Placental efficiency was reduced in obese dams, with increased calcification and reduced labyrinthine area. Consequently, fetuses from obese dams weighed less (P < 0.001) at the end of gestation. Despite normalisation of maternal parameters, metformin did not correct placental structure or fetal growth restriction. Metformin levels were substantial in the placenta and fetal circulation (109.7 ± 125.4 nmol g−1 in the placenta and 2063 ± 2327 nM in fetal plasma). These findings reveal the distinct effects of metformin administration during pregnancy on mother and fetus and highlight the complex balance of risk vs. benefits that are weighed in obstetric medical treatments. Key points: Maternal obesity and gestational diabetes mellitus have detrimental short‐ and long‐term effects for mother and child.Metformin is commonly used to treat gestational diabetes mellitus in many populations worldwide but the effects on fetus and placenta are unknown.In a mouse model of diet‐induced obesity and glucose intolerance in pregnancy we show reduced uterine artery compliance, placental structural changes and reduced fetal growth.Metformin treatment improved maternal metabolic health and uterine artery compliance but did not rescue obesity‐induced changes in the fetus or placenta. Metformin crossed the placenta into the fetal circulation and entered fetal tissue.Metformin has beneficial effects on maternal health beyond glycaemic control. However, despite improvements in maternal physiology, metformin did not prevent fetal growth restriction or placental ageing. The high uptake of metformin into the placental and fetal circulation highlights the potential for direct immediate effects of metformin on the fetus with possible long‐term consequences postnatally. [ABSTRACT FROM AUTHOR]

Compelling evidence exists indicating that developmental programming influences ageing. Programming alters life‐course phenotype in multiple organs, predisposing to diseases such as diabetes, obesity and cardiovascular disease that shorten lifespan. This review describes studies in rodents, the most commonly studied species, addressing interactions of programming challenges with ageing. We first consider ageing and programming of insulin function that has been clearly shown to decrease with age. It is important to evaluate ageing in pancreatic islets isolated from other systems. Studies discussed show premature pancreatic islet ageing resulting from both maternal under‐ and overnutrition. New ways to determine programming of adipose tissue and effects on fat storage are explored. Oxidative stress is a major factor that regulates ageing in tissues. Oxidative stress is discussed in relation to reproductive and cardiovascular ageing. Premature ageing is associated with both low and high glucocorticoid function. Both over and undernutrition have offspring sex‐specific programming effects on life‐course glucocorticoid concentrations. Evidence is provided that maternal age at conception affects offspring endocrine and metabolism ageing. Finally, the importance of matching foetal nutrition and energy availability with composition and energy content in the post‐weaning diet is demonstrated. This mismatch can lead to a greatly shortened lifespan. General principles are discussed throughout. For example, sexual dimorphism of age‐related outcomes can be marked. Accelerated ageing occurs early in life. Improving knowledge on programming ageing interactions will improve health span as well as lifespan. Finally, there are considerable similarities in outcomes programmed by maternal undernutrition and overnutrition. [ABSTRACT FROM AUTHOR]

Asthma is a common lung condition that makes breathing difficult through the inflammation and constriction of the lung airways. Epidemiological evidence supports the presence of a positive association between prenatal maternal psychological stress (PMPS) and asthma in the offspring, suggesting the disease may have developmental origins. T‐helper 2 (Th2) cells are a major subtype of T‐helper cells, producing Th2 cytokines, which may be the main drivers of asthma symptoms. A Th2 dominant blood cytokine profile may therefore indicate an increased risk of asthma, as studies have shown a link between PMPS and a T‐helper 2 (Th2) cytokine profile in offspring. The mechanism by which PMPS may cause Th2 cytokine dominance in the offspring is unclear. Epigenetic modifications in utero can lead to long‐lasting effects that persist postnatally and have therefore been implicated in this relationship. Increased maternal blood cortisol levels due to PMPS may increase transfer of cortisol to the foetus, where the temporarily increased levels may induce changes in the epigenome. Evidence from animal studies suggests that genes controlling cytokine production in T cells can be epigenetically modified in a way that increases Th2 cytokine production. Other evidence suggests that methylation of the NR3C1 gene decreases hippocampal glucocorticoid receptor expression, leading to decreased negative regulation of the hypothalamus‐pituitary‐adrenal axis. This can increase cortisol production which has been shown to increase Th2 cytokine production. Therefore, the link between PMPS and a Th2 offspring cytokine profile, mediated through epigenetic changes, may explain the positive relationship between PMPS and asthma in the offspring. [ABSTRACT FROM AUTHOR]

Early life adversity is a risk factor for psychiatric disorders, yet the mechanisms by which adversity increases this risk are still being delineated. Here, we used a limited bedding and nesting (LBN) manipulation in rats that models a low resource environment to examine effects on growth, developmental milestones, and endocrine endpoints. In LBN, dams and pups, from pups' postnatal days 2–9, are exposed to an environment where dams lack proper materials to build a nest. This manipulation is compared to control housing conditions, where rat dams have access to ample nesting materials and enrichment throughout pups' development. We found that the LBN condition altered maternal care, increasing pup‐directed behaviors while reducing self‐care. This, perhaps compensatory, increase in nursing and attention to pups did not mitigate against changes in metabolism, as LBN reduced weight gain in both sexes and this effect persisted into adulthood. Although adult stress hormone levels in both sexes and vaginal opening and estrous cycle length in females were not disrupted, there was other evidence of endocrine dysregulation. Compared to controls, LBN rats of both sexes had shortened anogenital distances, indicating reduced androgen exposure. LBN males also had higher plasma estradiol levels in adulthood. This combination of results suggests that LBN causes a demasculinizing effect in males that could contribute to lasting changes in the brain and behavior. Importantly, alterations in metabolic and endocrine systems due to early life adversity could be one mechanism by which stress early in life increases risk for later disease. [ABSTRACT FROM AUTHOR]

Obesity during pregnancy has been shown to increase the risk of metabolic diseases in the offspring. However, the factors within the maternal milieu which affect offspring phenotypes and the underlying mechanisms remain unknown. The adipocyte hormone leptin plays a key role in regulating energy homeostasis and is known to participate in sex‐specific developmental programming. To examine the action of leptin on fetal growth, placental gene expression and postnatal offspring metabolism, we injected C57BL mice with leptin or saline on gestational day 12 and then measured body weights (BWs) of offspring fed on a standard or obesogenic diet, as well as mRNA expression levels of insulin‐like growth factors and glucose and amino acid transporters. Male and female offspring born to leptin‐treated mothers exhibited growth retardation before and a growth surge after weaning. Mature male offspring, but not female offspring, exhibited increased BWs on a standard diet. Leptin administration prevented the development of hyperglycaemia in the obese offspring of both sexes. The placentas of the male and female foetuses differed in size and gene expression, and leptin injection decreased the fetal weights of both sexes, the placental weights of the male foetuses and placental gene expression of the GLUT1 glucose transporter in female foetuses. The data suggest that mid‐pregnancy is an ontogenetic window for the sex‐specific programming effects of leptin, and these effects may be exerted via fetal sex‐specific placental responses to leptin administration. [ABSTRACT FROM AUTHOR]

The article discusses the risk of obesity during pregnancy and metabolic complications and across large populations the rates of maternal obesity increased. Resveratrol is suggested as detrimental to normal fetal adrenal development which increases insulin sensitivity, promotes postpartum weight loss, and reduces adipose tissue mass in the obese mother. Also, the article focuses on the effect of maternal obesity on the social aspects of child development.

Key points: Maternal obesity predisposes to metabolic dysfunction in male and female offspringMaternal high‐fat diet consumption prior to and throughout pregnancy and lactation accelerates offspring metabolic ageing in a sex‐dependent mannerThis study provides evidence for programming‐ageing interactions Human epidemiological studies show that maternal obesity (MO) shortens offspring life and health span. Life course cellular mechanisms involved in this developmental programming‐ageing interaction are poorly understood. In a well‐established rat MO model, female Wistar rats ate chow (controls (C)) or high energy, obesogenic diet to induce MO from weaning through pregnancy and lactation. Females were bred at postnatal day (PND) 120. Offspring (F1) of mothers on control diet (CF1) and MO diet (MOF1) delivered spontaneously at terms. Both CF1 and MOF1 ate C diet from weaning throughout the study. Offspring were killed at PND 36, 110, 450 and 650. We determined body and liver weights, liver and serum metabolite concentrations, hormones and oxidative stress biomarkers. Male and female CF1 body weight, total fat, adiposity index, serum leptin, insulin, insulin resistance, and liver weight, fat, triglycerides, malondialdehyde, reactive oxygen species and nitrotyrosine all rose with differing ageing trajectories. Female CF1 triglycerides were unchanged with age. Age‐related increases were greater in MOF1 than CF1 in both sexes for all variables except glucose in males and females and cholesterol in males. Cholesterol fell in CF1 females but not MOF1. Serum corticosterone levels were higher in male and female MOF1 than CF1 and declined with age. DHEA serum levels were lower in male and female MOF1 than CF1. Liver antioxidant enzymes decreased with age (CF1 and MOF1). Conclusions: exposure to the developmental challenge of MO accelerates progeny ageing metabolic and endocrine profiles in a sex specific manner, providing evidence for programming‐ageing interactions. Key points: Maternal obesity predisposes to metabolic dysfunction in male and female offspringMaternal high‐fat diet consumption prior to and throughout pregnancy and lactation accelerates offspring metabolic ageing in a sex‐dependent mannerThis study provides evidence for programming‐ageing interactions [ABSTRACT FROM AUTHOR]

At the Prenatal Programming and Toxicity (PPTox) Conference I in 2008, I presented an overview of the developmental origins of health and disease field focusing on environmental chemical exposures and disease outcomes. At that time, I noted that the field was getting off the ground with a focus on developmental exposure to a small number of endocrine disrupting chemicals (EDCs) and disease outcomes across the lifespan in animal models. In this update, I note that the DOHaD field has changed significantly over the last decade. There are new windows of susceptibility including preconception, prepuberty, a focus on the mother and not just the offspring, and a significant focus on the new field of epigenetic transgenerational inheritance. New disease focus areas have sprung up including obesity, type 2 diabetes and fatty liver disease, all with a connection to developmental exposures to EDCs. There is also a focus on the study of new EDCs, molecular mechanisms, the development of new biomarkers of exposure and disease outcomes and studies focusing on intervention and prevention studies. [ABSTRACT FROM AUTHOR]

Background: Non‐human primate models of developmental programming by maternal obesity (MO) are needed for translation to human programming outcomes. We present baboon offspring (F1) morphometry, blood cortisol, and adrenocorticotropic hormone (ACTH) from 0.9 gestation to 0‐2 years. Methods: Control mothers ate chow; MO mothers ate high‐fat high‐energy diet pre‐pregnancy through lactation. Results: Maternal obesity mothers weighed more than controls pre‐pregnancy. Maternal obesity gestational weight gain was lower with no correlation with fetal or placenta weights. At 0.9 gestation, MO and control F1 morphometry and ACTH were similar. MO‐F1 0.9 gestation male cortisol was lower, rising slower from 0‐2 years vs control‐F1. At birth, male MO‐F1 and control‐F1 weights were similar, but growth from 0‐2 years was steeper in MO‐F1; newborn female MO‐F1 weighed more than control‐F1 but growth from 0‐2 years was similar. ACTH did not change in either sex. Conclusions: Maternal obesity produced sexually dimorphic fetal and postnatal growth and hormonal phenotypes. [ABSTRACT FROM AUTHOR]

Summary: Cryptosporidiosis causes persistent diarrhoea in infants, immunocompromised patients and elderly persons. Long‐term consequences of the disease include increased risk of malignancy, cardiomyopathy and gastrointestinal inflammation. This study aimed to investigate prolonged effects of cryptosporidiosis on innate immunity and growth in neonatal C3HA mice. The disease was challenged by Cryptosporidium parvum oocyst inoculation into 7‐day‐old animals. The mice whose intestine smears contained 3‐5 or 6 and more oocysts per microscopic field at the day 5 after infection were considered as mildly or severely infected, correspondingly. To determine natural killer cell (NK) activity, we applied 3H‐uridine cytotoxic assay to the animals at 5‐68 days after infection using K562 cells as targets. At severe infection, there was a statistically significant 1.5‐2.0 fold decline of body mass, spleen mass and spleen cellularity that persisted in animals of all ages. Accordingly, NK cytotoxicity showed even more drastic drop reaching 2.7‐3.0 folds that was statistically significant in all animals. At mild infection, the discovered effects were less pronounced and reached significance only in some age groups. Thus, our study provides evidence that NK cells show long‐term cytotoxic activity decrease following Cryptosporidium infection in neonatal mice, particularly in severe disease. [ABSTRACT FROM AUTHOR]

Background Most developmental programming studies on maternal nutrient reduction ( MNR) are in altricial rodents whose maternal nutritional burden and offspring developmental trajectory differ from precocial non-human primates and humans. Methods Control ( CTR) baboon mothers ate ad libitum; MNR mothers ate 70% global control diet in pregnancy and lactation. Results We present offspring morphometry, blood cortisol, and adrenocorticotropin ( ACTH) during second half of gestation (G) and first three postnatal years. Moderate MNR produced intrauterine growth restriction ( IUGR). IUGR males (n=43) and females (n=28) were smaller than CTR males (n=50) and females (n=47) in many measurements at many ages. In CTR, fetal ACTH increased 228% and cortisol 48% between 0.65G and 0.9G. IUGR ACTH was elevated at 0.65G and cortisol at 0.9G. 0.9G maternal gestational weight gain, fetal weight, and placenta weight were correlated. Conclusions Moderate IUGR decreased body weight and morphometric measurements at key time points and altered hypothalamo-pituitary-adrenal function. [ABSTRACT FROM AUTHOR]

Being born at an extremely low birth weight (ELBW; <1,000 grams) is presumed to reflect a suboptimal intrauterine environment and thus presents an opportunity for examining developmental programming hypotheses. Interfacing prenatal programming and differential susceptibility hypotheses, we tested whether individuals with ELBW in different childhood rearing environments showed different attention biases to positive and negative facial emotions in adulthood. Using the oldest known, prospectively followed cohort of ELBW survivors, we found that relative to normal birth weight controls (NBW; >2,500 grams), ELBW survivors displayed the highest and lowest attention bias to happy faces at age 30-35, depending on whether their total family income at age 8 was relatively low (environmental match) or high (environmental mismatch), respectively. This bias to happy faces was associated with a reduced likelihood of emotional problems. Findings suggest that differential susceptibility to positive emotions may be prenatally programmed, with effects lasting into adulthood. We discuss implications for integrating prenatal programming and differential susceptibility hypotheses, and the developmental origins of postnatal plasticity and resilience. [ABSTRACT FROM AUTHOR]

Key points Fructose-containing sugars, including sucrose and high fructose corn syrup (HFCS), have been implicated in the epidemics of obesity and type 2 diabetes., Few studies have evaluated the impact of perinatal exposure to these sugars on metabolic and physiological outcomes in the offspring., Using a rat model, offspring exposed to a maternal sucrose or HFCS diet during the prenatal and/or suckling periods were found to have altered adiposity and liver fat content and composition at weaning., Plasma levels of free fatty acids remained elevated in young adulthood, but consumption of a control diet following weaning appeared to ameliorate most other effects of perinatal exposure to a maternal high-sugar diet., Guidelines for maternal nutrition should advise limiting consumption of fructose-containing sugars, and it is particularly important that these recommendations include maternal nutrition during lactation., Abstract Perinatal exposure to excess maternal intake of added sugars, including fructose and sucrose, is associated with an increased risk of obesity and type 2 diabetes in adult life. However, it is unknown to what extent the type of sugar and the timing of exposure affect these outcomes. The aim of this study was to determine the impact of exposure to maternal consumption of a 10% (w/v) beverage containing sucrose or high fructose corn syrup-55 (HFCS-55) during the prenatal and/or suckling periods on offspring at 3 and 12 weeks, utilising a cross-fostering approach in a rodent model. Perinatal sucrose exposure decreased plasma glucose concentrations in offspring at 3 weeks, but did not alter glucose tolerance. Increased adiposity was observed in 3-week-old offspring exposed to sucrose or HFCS-55 during suckling, with increased hepatic fat content in HFCS-55-exposed offspring. In terms of specific fatty acids, hepatic monounsaturated (omega-7 and -9) fatty acid content was elevated at weaning, and was most pronounced in sucrose offspring exposed during both the prenatal and suckling periods, and HFCS-55 offspring exposed during suckling only. By 12 weeks, the effects on adiposity and hepatic lipid composition were largely normalised. However, exposure to either sucrose or HFCS-55 during the prenatal period only was associated with elevated plasma free fatty acids at weaning, and this effect persisted until 12 weeks. This study suggests that the type of sugar and the timing of exposure (prenatal or suckling periods) are both important for determining the impact on metabolic health outcomes in the offspring. [ABSTRACT FROM AUTHOR]

ABSTRACT Maternal nutrition can have long-term effects on offspring morphology, physiology and behaviours. However, it is unclear whether mothers 'program' offspring behavioural coping strategy (proactive/reactive) according to the predicted nutritional quality of their future environment. We conducted a systematic review on this topic and meta-analytically synthesized relevant experimental data on mice and rats (46 studies). We included data from experiments where dams were subjected to caloric restriction, protein restriction or overfeeding around gestation and subsequently measured offspring activity, exploration, or anxiety. Overall, little evidence existed for effects of maternal nutrition on the three investigated behavioural traits. The high heterogeneity observed in the data set suggests that maternal programming may sometimes occur. However, because offspring had access to a balanced diet before testing, behaviours may have been reprogrammed. Our results may indicate that reprogrammed behaviours could ameliorate negative effects associated with sub-optimal nutrition in early life. Further, our systematic review revealed clear knowledge gaps and fruitful future research avenues. [ABSTRACT FROM AUTHOR]

Skeletal muscle mass, quality and adaptability are fundamental in promoting muscle performance, maintaining metabolic function and supporting longevity and healthspan. Skeletal muscle is programmable and can 'remember' early-life metabolic stimuli affecting its function in adult life. In this review, the authors pose the question as to whether skeletal muscle has an 'epi'-memory? Following an initial encounter with an environmental stimulus, we discuss the underlying molecular and epigenetic mechanisms enabling skeletal muscle to adapt, should it re-encounter the stimulus in later life. We also define skeletal muscle memory and outline the scientific literature contributing to this field. Furthermore, we review the evidence for early-life nutrient stress and low birth weight in animals and human cohort studies, respectively, and discuss the underlying molecular mechanisms culminating in skeletal muscle dysfunction, metabolic disease and loss of skeletal muscle mass across the lifespan. We also summarize and discuss studies that isolate muscle stem cells from different environmental niches in vivo (physically active, diabetic, cachectic, aged) and how they reportedly remember this environment once isolated in vitro. Finally, we will outline the molecular and epigenetic mechanisms underlying skeletal muscle memory and review the epigenetic regulation of exercise-induced skeletal muscle adaptation, highlighting exercise interventions as suitable models to investigate skeletal muscle memory in humans. We believe that understanding the 'epi'-memory of skeletal muscle will enable the next generation of targeted therapies to promote muscle growth and reduce muscle loss to enable healthy aging. [ABSTRACT FROM AUTHOR]

Mother-child cohort studies have established that both pre-pregnancy body mass index ( BMI) and gestational weight gain are independently associated with cardio-metabolic risk factors in young adult offspring, including systolic and diastolic blood pressure. Animal models in sheep and non-human primates provide further evidence for the influence of maternal obesity on offspring cardiovascular function, whilst recent studies in rodents suggest that perinatal exposure to the metabolic milieu of maternal obesity may permanently change the central regulatory pathways involved in blood pressure regulation. Leptin plays an important role in the central control of appetite, is also involved in activation of efferent sympathetic pathways to both thermogenic and non-thermogenic tissues, such as the kidney, and is therefore implicated in obesity-related hypertension. Leptin is also thought to have a neurotrophic role in the development of the hypothalamus, and altered neonatal leptin profiles secondary to maternal obesity are associated with permanently altered hypothalamic structure and function. In rodent studies, maternal obesity confers persistent sympathoexcitatory hyper-responsiveness and hypertension acquired in the early stages of development. Experimental neonatal hyperleptinaemia in naive rat pups provides further evidence of heightened sympathetic tone and proof of principle that hyperleptinaemia during a critical window of hypothalamic development may directly lead to adulthood hypertension. Insight from these animal models raises the possibility that early-life exposure to leptin in humans may lead to early onset essential hypertension. Ongoing mother-child cohort and intervention studies in obese pregnant women provide a unique opportunity to address associations between maternal obesity and offspring cardiovascular function. The goal of the review is to highlight the potential importance of leptin in the developmental programming of hypertension in obese pregnancy. [ABSTRACT FROM AUTHOR]

Preterm birth affects 8-10% of human pregnancies and is a major cause of long-term disability. Individuals who are born very preterm, especially if they develop bronchopulmonary dysplasia ( BPD), have an increased risk of impaired lung function in infancy, childhood and adulthood, as well as an increased risk of respiratory illness. Our aim is to briefly review current understanding of the basis for long-term impairments in lung function and respiratory health following preterm birth and BPD., Histopathology of the lungs of infants and children following preterm birth and BPD shows altered development of the lung parenchyma, conducting airways and pulmonary vasculature. Owing to improvements in the care of preterm infants, especially the use of exogenous surfactant and lower concentrations of administered oxygen, lung pathology following preterm birth and BPD is less severe than in the past., Recent studies indicate that very preterm birth and BPD can lead to hyperplasia of airway smooth muscle, impaired alveolarization, pulmonary inflammation and an increase in pulmonary artery muscularization. Imaging of adult lungs suggests that the deficit in alveoli can persist into later life. Long-term lung injury apparently relates to the use of mechanical ventilation and the use of supplemental oxygen in infancy., Impaired lung function in later life is due to airway hyper-reactivity and fewer alveoli, resulting in reductions in the surface area for gas exchange and physical support for bronchioles. Because the incidence of preterm birth is not declining, it will continue to be a major cause of respiratory ill-health in adults. [ABSTRACT FROM AUTHOR]

Nutritional influences on cardiovascular disease operate throughout life. Studies in both experimental animals and humans have suggested that changes in the peri- and early post-natal nutrition can affect the development of the various components of the metabolic syndrome in adult life. This has lead to the hypothesis that n-3 fatty acid supplementation in pregnancy may have a beneficial effect on lipid profile in the offspring. The aim of the present study was to investigate the effect of supplementation with n-3 fatty acids during the third trimester of pregnancy on lipids and lipoproteins in the 19-year-old offspring. The study was based on the follow-up of a randomized controlled trial from 1990 where 533 pregnant women were randomized to fish oil ( n = 266), olive oil ( n = 136) or no oil ( n = 131). In 2009, the offspring were invited to a physical examination including blood sampling. A total of 243 of the offspring participated. Lipid values did not differ between the fish oil and olive oil groups. The relative adjusted difference (95% confidence intervals) in lipid concentrations was −3% (−11; 7) for LDL cholesterol, 3% (−3; 10) for HDL cholesterol, −1% (−6; 5) for total cholesterol,−4% (−16; 10) for TAG concentrations, 2%(−2; 7) for apolipoprotein A1, −1% (−9; 7) for apolipoprotein B and 3% (−7; 15) in relative abundance of small dense LDL. In conclusion, there was no effect of fish oil supplementation during the third trimester of pregnancy on offspring plasma lipids and lipoproteins in adolescence. [ABSTRACT FROM AUTHOR]

Animals have evolved diverse protective mechanisms for responding to toxic chemicals of both natural and anthropogenic origin. From a governmental regulatory perspective, these protective responses complicate efforts to establish acceptable levels of chemical exposure. To explore this issue, we considered vertebrate endocrine systems as potential targets for environmental contaminants. Using the hypothalamic-pituitary-thyroid (HPT), hypothalamic-pituitary-gonad (HPG), and hypothalamic-pituitary-adrenal (HPA) axes as case examples, we identified features of these systems that allow them to accommodate and recover from chemical insults. In doing so, a distinction was made between effects on adults and those on developing organisms. This distinction was required because endocrine system disruption in early life stages may alter development of organs and organ systems, resulting in permanent changes in phenotypic expression later in life. Risk assessments of chemicals that impact highly regulated systems must consider the dynamics of these systems in relation to complex environmental exposures. A largely unanswered question is whether successful accommodation to a toxic insult exerts a fitness cost on individual animals, resulting in adverse consequences for populations. Mechanistically based mathematical models of endocrine systems provide a means for better understanding accommodation and recovery. In the short term, these models can be used to design experiments and interpret study findings. Over the long term, a set of validated models could be used to extrapolate limited in vitro and in vivo testing data to a broader range of untested chemicals, species, and exposure scenarios. With appropriate modification, Tier 2 assays developed in support of the U.S. Environmental Protection Agency's Endocrine Disruptor Screening Program could be used to assess the potential for accommodation and recovery and inform the development of mechanistically based models. Environ. Toxicol. Chem. 2011;30:39-51. © 2010 SETAC [ABSTRACT FROM AUTHOR]

Objective Maternal hypercholesterolaemia during pregnancy increases lipid peroxidation in mothers and fetuses and programs increased susceptibility to atherosclerosis later in life. The objective of this study was to elucidate the role of the placenta in mediating oxidative stress from mother to offspring. Design Comparison between normo- and hypercholesterolaemic mothers ( n = 36 each) and their children. Setting Obstetric wards, hospitals of the University of Naples and Regione Campania. Population Healthy primiparas delivering by caesarean section. Methods Biochemical measurements of oxidative stress and serum leptin in cord plasma and placenta, immunochemistry of placenta microvessels, and vasoreactivity studies were performed. Main outcome measures Oxidative status (i.e. lipid composition and content of oxidised fatty acids, activity of pro- and antioxidant enzymes, immunohistochemical presence of oxidation-specific epitopes) in maternal and cord blood and in placental tissue, as well as vascular reactivity in omental arteries. Results Hypercholesterolaemia during pregnancy was associated with extensive changes in fatty acid composition of both maternal and cord blood lipids, sufficient to alter vasoreactivity of omental vessels. Results also indicated that the placenta is not only subject to substantial oxidative stress, but that it may further increase fetal oxidative stress through changes of pro- and antioxidant enzyme activities. Conclusions The placenta plays an important role in both transmitting and enhancing pathogenic effects of gestational hypercholesterolaemia. [ABSTRACT FROM AUTHOR]

Now that analysis of the organization of the human genome sequence is reaching completion, studies of the finely tuned chromatin epigenetic networks, DNA methylation and histone modifications, are required to determine how the same DNA sequence generates different cells, lineages and organs, i.e. the phenotype. Maternal nutrition, behaviour and metabolic disturbances as well as other environmental factors have been shown to have major effects on these epigenetic processes, potentially affecting the predisposition of offspring to obesity and related adult disorders. The March 2006 Stock Conference considered the latest evidence from studies in the field of obesity and other related areas that elucidate mechanisms by which the environment can modify gene expression and the resulting individual phenotype. Presentations included evaluation of the molecular basis of epigenetic memory and the nature of relevant sequence targets, windows of susceptibility, and maternal dietary and behavioural factors that determine epigenetic changes. Imprinted genes, age and tissue-related exposures, transgenerational and potential interventions were also discussed. In summary, it is clear that epigenetic alterations can no longer be ignored in evaluations of the causes of obesity and its associated disorders. There is a need for systematic large-scale epigenetic studies of obesity, employing appropriate strategies and techniques and appropriately chosen environmental factors in critical spatio-temporal windows. [ABSTRACT FROM AUTHOR]

This study was conducted to determine the impact of dried distiller's grain with solubles (DDGS) from 192 days of gestation through 118 days of lactation on feedlot performance, carcass characteristics, Longissimus muscle (LM) fatty acids and glucose tolerance of male progeny ( n = 36). Angus-Simmental heifer dams were fed diets that contained either DDGS (DG) or not (CON) formulated to provide similar daily net energy for gain but differing crude protein. In the feedlot, male progeny were fed a diet devoid of DDGS. An intravenous glucose tolerance test (IVGTT) was performed on a subset of 20 steers prior to harvest. Steers were harvested at a common 12th rib fat depth. Data were analyzed with the GLIMMIX and MIXED procedures of SAS. Performance ( P ≥ 0.11) and glucose and insulin concentrations during IVGTT ( P ≥ 0.24) did not differ between treatments. Dressing percentage tended to be greater ( P = 0.09) in DG than CON progeny, but all other carcass characteristics did not differ ( P ≥ 0.18). Progeny from DG dams had greater LM 16:2, 18:0, and 20:1 n-9 concentrations than progeny from CON dams ( P ≤ 0.02). In conclusion, DDGS are a viable option for gestating and lactating beef cows. [ABSTRACT FROM AUTHOR]