Long-Term Programming of CD8 T Cell Immunity by Perinatal Exposure to Glucocorticoids.

Early life environmental exposure, particularly during perinatal period, can have a life-long impact on organismal development and physiology. The biological rationale for this phenomenon is to promote physiological adaptations to the anticipated environment based on early life experience. However, perinatal exposure to adverse environments can also be associated with adult-onset disorders. Multiple environmental stressors induce glucocorticoids, which prompted us to investigate their role in developmental programming. Here, we report that perinatal glucocorticoid exposure had long-term consequences and resulted in diminished CD8 T cell response in adulthood and impaired control of tumor growth and bacterial infection. We found that perinatal glucocorticoid exposure resulted in persistent alteration of the hypothalamic-pituitary-adrenal (HPA) axis. Consequently, the level of the hormone in adults was significantly reduced, resulting in decreased CD8 T cell function. Our study thus demonstrates that perinatal stress can have long-term consequences on CD8 T cell immunity by altering HPA axis activity.

The Metabolically Obese, Normal-Weight Phenotype in Young Rats Is Associated with Cognitive Impairment and Partially Preventable with Leptin Intake during Lactation.

The intake of high-fat diets (HFDs) and obesity are linked to cognitive impairment. Here, we aimed to investigate whether an early metabolically obese, normal-weight (MONW) phenotype, induced with an HFD in young rats, also leads to cognitive dysfunction and to evaluate the potential cognitive benefits of neonatal intake of leptin. To achieve this, Wistar rats orally received physiological doses of leptin or its vehicle during lactation, followed by 11 weeks of pair-feeding with an HFD or control diet post-weaning. Working memory was assessed using a T-maze, and gene expression in the hippocampus and peripheral blood mononuclear cells (PBMCs) was assessed with real-time RT-qPCR to identify cognition biomarkers. Young MONW-like rats showed hippocampal gene expression changes and decreased working memory. Animals receiving leptin during lactation presented similar gene expression changes but preserved working memory despite HFD intake, partly due to improved insulin sensitivity. Notably, PBMC Syn1 expression appears as an accessible biomarker of cognitive health, reflecting both the detrimental effect of HFD intake at early ages despite the absence of obesity and the positive effects of neonatal leptin treatment on cognition. Thus, the MONW phenotype developed at a young age is linked to cognitive dysfunction, which is reflected at the transcriptomic level in PBMCs. Neonatal leptin intake can partly counteract this impaired cognition resulting from early HFD consumption.

Elevated n-3/n-6 PUFA ratio in early life diet reverses adverse intrauterine kidney programming in female rats.

Intrauterine growth restriction (IUGR) predisposes to chronic kidney disease via activation of proinflammatory pathways, and omega-3 PUFAs (n-3 PUFAs) have anti-inflammatory properties. In female rats, we investigated 1) how an elevated dietary n-3/n-6 PUFA ratio (1:1) during postnatal kidney development modifies kidney phospholipid (PL) and arachidonic acid (AA) metabolite content and 2) whether the diet counteracts adverse molecular protein signatures expected in IUGR kidneys. IUGR was induced by bilateral uterine vessel ligation or intrauterine stress through sham operation 3.5 days before term. Control (C) offspring were born after uncompromised pregnancy. On postnatal (P) days P2-P39, rats were fed control (n-3/n-6 PUFA ratio 1:20) or n-3 PUFA intervention diet (N3PUFA; ratio 1:1). Plasma parameters (P33), kidney cortex lipidomics and proteomics, as well as histology (P39) were studied. We found that the intervention diet tripled PL-DHA content (PC 40:6; P < 0.01) and lowered both PL-AA content (PC 38:4 and lyso-phosphatidylcholine 20:4; P < 0.05) and AA metabolites (HETEs, dihydroxyeicosatrienoic acids, and epoxyeicosatrienoic acids) to 25% in all offspring groups. After ligation, our network analysis of differentially expressed proteins identified an adverse molecular signature indicating inflammation and hypercoagulability. N3PUFA diet reversed 61 protein alterations (P < 0.05), thus mitigating adverse IUGR signatures. In conclusion, an elevated n-3/n-6 PUFA ratio in early diet strongly reduces proinflammatory PLs and mediators while increasing DHA-containing PLs regardless of prior intrauterine conditions. Counteracting a proinflammatory hypercoagulable protein signature in young adult IUGR individuals through early diet intervention may be a feasible strategy to prevent developmentally programmed kidney damage in later life.

Maternal pregnancy weight or gestational weight gain and offspring's blood pressure: A systematic review.

AIMS: An increasing number of studies suggest that maternal weight parameters in pregnancy are associated with offspring's blood pressure (BP). The aim of this systematic review - following the updated Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) Statement - was to assess and judge the evidence for an association between maternal pregnancy weight/body mass index (BMI) or gestational weight gain (GWG) with offspring's BP in later life. DATA SYNTHESIS: MEDLINE, EMBASE, Cochrane Library, CINAHL and Web of Science were searched without limits. Risk of bias was assessed using the "US National Heart, Lung and Blood Institute"-tool, and an evidence grade was allocated following the "World Cancer Research Fund" criteria. Of 7,124 publications retrieved, 16 studies (all cohort studies) were included in the systematic review. Overall data from 52,606 participants (0 years [newborns] to 32 years) were enclosed. Association between maternal pregnancy BMI and offspring's BP were analyzed in 2 (both "good-quality" rated) studies, without consistent results. GWG and offspring's BP was analyzed in 14 studies (2 "good-quality", 9 "fair-quality", 3 "poor-quality" rated). Of these, 3 "fair-quality" studies described significant positive results for systolic BP and significant results, but partly with varying directions of effect estimates for diastolic BP. Mean arterial pressure (MAP) was analyzed in 1 "poor-quality" congress paper. Overall, based on the small number of "good-quality"-rated studies and the inconsistency of effect direction, no firm conclusion can be drawn. CONCLUSION: Evidence for an association of maternal pregnancy weight determinants with offspring's BP was overall graded as "limited - no conclusion".

Analysis of Both Lipid Metabolism and Endocannabinoid Signaling Reveals a New Role for Hypothalamic Astrocytes in Maternal Caloric Restriction-Induced Perinatal Programming.

Maternal malnutrition in critical periods of development increases the risk of developing short- and long-term diseases in the offspring. The alterations induced by this nutritional programming in the hypothalamus of the offspring are of special relevance due to its role in energy homeostasis, especially in the endocannabinoid system (ECS), which is involved in metabolic functions. Since astrocytes are essential for neuronal energy efficiency and are implicated in brain endocannabinoid signaling, here we have used a rat model to investigate whether a moderate caloric restriction (R) spanning from two weeks prior to the start of gestation to its end induced changes in offspring hypothalamic (a) ECS, (b) lipid metabolism (LM) and/or (c) hypothalamic astrocytes. Monitorization was performed by analyzing both the gene and protein expression of proteins involved in LM and ECS signaling. Offspring born from caloric-restricted mothers presented hypothalamic alterations in both the main enzymes involved in LM and endocannabinoids synthesis/degradation. Furthermore, most of these changes were similar to those observed in hypothalamic offspring astrocytes in culture. In conclusion, a maternal low caloric intake altered LM and ECS in both the hypothalamus and its astrocytes, pointing to these glial cells as responsible for a large part of the alterations seen in the total hypothalamus and suggesting a high degree of involvement of astrocytes in nutritional programming.

Maternal healthful dietary patterns during peripregnancy and long-term overweight risk in their offspring.

Adherence to healthful dietary patterns is associated with lower body mass index (BMI) in adults; however, whether maternal diet quality during peripregnancy is related to a lower overweight risk in the offspring remains to be elucidated. We investigated the associations between the Alternate Healthy Eating Index (AHEI), Alternate Mediterranean Diet (aMED) and Dietary Approach to Stop Hypertension (DASH) during peripregnancy and offspring weight outcomes in a study including 2729 mother-child pairs from the Nurses' Health Study II and offspring cohort Growing Up Today Study II. Children, 12-14 years at baseline were 21-23 years at the last follow-up. Overweight or obesity was defined according to International Obesity Task Force (< 18 years) and World-Health-Organization guidelines (18 + years). Maternal dietary patterns were calculated from food frequency questionnaires. Log-binomial models were used to estimate relative risks (RR) and 95% confidence intervals. In models adjusted for sex, gestational age at delivery and maternal total energy intake, greater maternal adherence to aMED and DASH, but not AHEI, was associated with lower overweight risk in the offspring (RRQ5 vs Q1 = 0.82 [0.70-0.97] for aMED and 0.86 [0.72-1.04] for DASH, P for trend < 0.05 for both). After additional adjustment for maternal pre-pregnancy lifestyle factors and socio-demographic characteristic, none of the diet quality scores were significantly associated with offspring overweight risk. Maternal pre-pregnancy BMI did not modify any of these associations. In this population of generally well-nourished women, maternal healthful dietary patterns during the period surrounding pregnancy were not independently associated with offspring overweight risk at ages 12-23 years.

Perinatal fluoxetine treatment promotes long-term behavioral changes in adult mice.

Serotonin exerts a significant role in the mammalian central nervous system embryogenesis and brain ontogeny. Therefore, we investigate the effect of perinatal fluoxetine (FLX), a selective serotonin reuptake inhibitor, administration on the behavioral expression of adult male Swiss mice. For this purpose, two groups (n = 6 each, and ~ 35 g) of pregnant female Swiss mice were mated. Their offspring were treated with FLX (10 mg/Kg, s.c.) from postnatal day (PND) 5 to 15. At PND 16, one male puppy of each litter was euthanized, and the hippocampus was dissected for RNA analysis. At 70 days of life, the male offspring underwent a behavioral assessment in the open field, object recognition task, light-dark box, tail suspension and rotarod test. According to our results, the programmed animals had a decrease in TPH2, 5HT1a, SERT, BDNF, and LMX1B expression. Also, it was observed less time of immobility in tail suspension test and higher grooming time in the open field test. In the light-dark box test, the FLX-treated offspring had less time in the light side than control. We also observed a low cognitive performance in the object recognition task and poor motor skill learning in the rotarod test. These findings suggest that programming with FLX during the neonatal period alters a hippocampal serotonergic system, promoting anxiety and antidepressant behavior in adults, as well as a low mnemonic capacity.

Programming of Cardiovascular Dysfunction by Postnatal Overfeeding in Rodents.

Nutritional environment in the perinatal period has a great influence on health and diseases in adulthood. In rodents, litter size reduction reproduces the effects of postnatal overnutrition in infants and reveals that postnatal overfeeding (PNOF) not only permanently increases body weight but also affects the cardiovascular function in the short- and long-term. In addition to increased adiposity, the metabolic status of PNOF rodents is altered, with increased plasma insulin and leptin levels, associated with resistance to these hormones, changed profiles and levels of circulating lipids. PNOF animals present elevated arterial blood pressure with altered vascular responsiveness to vasoactive substances. The hearts of overfed rodents exhibit hypertrophy and elevated collagen content. PNOF also induces a disturbance of cardiac mitochondrial respiration and produces an imbalance between oxidants and antioxidants. A modification of the expression of crucial genes and epigenetic alterations is reported in hearts of PNOF animals. In vivo, a decreased ventricular contractile function is observed during adulthood in PNOF hearts. All these alterations ultimately lead to an increased sensitivity to cardiac pathologic challenges such as ischemia-reperfusion injury. Nevertheless, caloric restriction and physical exercise were shown to improve PNOF-induced cardiac dysfunction and metabolic abnormalities, drawing a path to the potential therapeutic correction of early nutritional programming.

Mechanisms of Reciprocal Regulation of Gonadotropin-Releasing Hormone (GnRH)-Producing and Immune Systems: The Role of GnRH, Cytokines and Their Receptors in Early Ontogenesis in Normal and Pathological Conditions.

Different aspects of the reciprocal regulatory influence on the development of gonadotropin-releasing hormone (GnRH)-producing- and immune systems in the perinatal ontogenesis and their functioning in adults in normal and pathological conditions are discussed. The influence of GnRH on the development of the immune system, on the one hand, and the influence of proinflammatory cytokines on the development of the hypothalamic-pituitary-gonadal system, on the other hand, and their functioning in adult offspring are analyzed. We have focused on the effects of GnRH on the formation and functional activity of the thymus, as the central organ of the immune system, in the perinatal period. The main mechanisms of reciprocal regulation of these systems are discussed. The reproductive health of an individual is programmed by the establishment and development of physiological systems during critical periods. Regulatory epigenetic mechanisms of development are not strictly genetically controlled. These processes are characterized by a high sensitivity to various regulatory factors, which provides possible corrections for disorders.

Obesity is Associated with Higher Blood Pressure and Higher Levels of Angiotensin II but Lower Angiotensin-(1-7) in Adolescents Born Preterm.

OBJECTIVES: To evaluate if obesity is associated with increased angiotensin II (Ang II) and decreased angiotensin-(1-7) or Ang-(1-7) in the circulation and urine among adolescents born prematurely. STUDY DESIGN: In a cross-sectional analysis of 175 14-year-olds born preterm with very low birth weight, we quantified plasma and urinary Ang II and Ang-(1-7) and compared their levels between subjects with overweight/obesity (body mass index ≥85th percentile, n = 61) and those with body mass index <85th percentile (n = 114) using generalized linear models, adjusted for race and antenatal corticosteroid exposure. RESULTS: Overweight/obesity was associated with higher systolic blood pressure and a greater proportion with high blood pressure. After adjustment for confounders, overweight/obesity was associated with an elevated ratio of plasma Ang II to Ang-(1-7) (ß: 0.57, 95% CI 0.23-0.91) and higher Ang II (ß: 0.21 pmol/L, 95% CI 0.03-0.39) but lower Ang-(1-7) (ß: -0.37 pmol/L, 95% CI -0.7 to -0.04). Overweight/obesity was associated with a higher ratio of urinary Ang II to Ang-(1-7) (ß: 0.21, 95% CI -0.02 to 0.44), an effect that approached statistical significance. CONCLUSIONS: Among preterm-born adolescents, overweight/obesity was associated with increased Ang II but reduced Ang-(1-7) in the circulation and the kidney as well as higher blood pressure. Obesity may compound the increased risk of hypertension and cardiovascular disease in individuals born prematurely by further augmenting the prematurity-associated imbalance in the renin-angiotensin system.

Maternal Western diet during gestation and lactation modifies adult offspring's cognitive and hedonic brain processes, behavior, and metabolism in Yucatan minipigs.

This study explores the long-term effects of exposure to a maternal Western diet (WD) vs. standard diet (SD) in the Yucatan minipig, on the adult progeny at lean status ( n = 32), and then overweight status. We investigated eating behavior, cognitive abilities, brain basal glucose metabolism, dopamine transporter availability, microbiota activity, blood lipids, and glucose tolerance. Although both groups demonstrated similar cognitive abilities in a holeboard test, WD pigs expressed a higher stress level than did SD pigs (immobility, P < 0.05) and lower performance in an alley maze ( P = 0.06). WD pigs demonstrated lower dopamine transporter binding potential in the hippocampus and parahippocampal cortex ( P < 0.05 for both), as well as a trend in putamen ( P = 0.07), associated with lower basal brain activity in the prefrontal cortex and nucleus accumbens ( P < 0.05) compared with lean SD pigs. Lean WD pigs demonstrated a lower glucose tolerance than did SD animals (higher glucose peak, P < 0.05) and a tendency to a higher incremental area under the curve of insulin from 0 to 30 minutes after intravenous glucose injection ( P < 0.1). Both groups developed glucose intolerance with overweight, but WD animals were less impacted than SD animals. These results demonstrate that maternal diet shaped the offspring's brain functions and cognitive responses long term, even after being fed a balanced diet from weaning, but behavioral effects were only revealed in WD pigs under anxiogenic situation; however, WD animals seemed to cope better with the obesogenic diet from a metabolic standpoint.-Gautier, Y., Luneau, I., Coquery, N., Meurice, P., Malbert, C.-H., Guerin, S., Kemp, B., Bolhuis, J. E., Clouard, C., Le Huërou-Luron, I., Blat, S., Val-Laillet, D. Maternal Western diet during gestation and lactation modifies adult offspring's cognitive and hedonic brain processes, behavior, and metabolism in Yucatan minipigs.

Reduced PPARγ2 expression in adipose tissue of male rat offspring from obese dams is associated with epigenetic modifications.

According to the Developmental Origin of Health and Disease (DOHaD) concept, maternal obesity and accelerated growth in neonates program obesity later in life. White adipose tissue (WAT) has been the focus of developmental programming events, although underlying mechanisms remain elusive. In rodents, WAT development primarily occurs during lactation. We previously reported that adult rat offspring from dams fed a high-fat (HF) diet exhibited fat accumulation and decreased peroxisome proliferator-activated receptor γ (PPARγ) mRNA levels in WAT. We hypothesized that PPARγ down-regulation occurs via epigenetic malprogramming which takes place during adipogenesis. We therefore examined epigenetic modifications in the PPARγ1 and PPARγ2 promoters in perirenal (pWAT) and inguinal fat pads of HF offspring at weaning (postnatal d 21) and in adulthood. Postnatal d 21 is a period characterized by active epigenomic remodeling in the PPARγ2 promoter (DNA hypermethylation and depletion in active histone modification H3ac and H3K4me3) in pWAT, consistent with increased DNA methyltransferase and DNA methylation activities. Adult HF offspring exhibited sustained hypermethylation and histone modification H3ac of the PPARγ2 promoter in both deposits, correlated with persistent decreased PPARγ2 mRNA levels. Consistent with the DOHaD hypothesis, retained epigenetic marks provide a mechanistic basis for the cellular memory linking maternal obesity to a predisposition for later adiposity.-Lecoutre, S., Pourpe, C., Butruille, L., Marousez, L., Laborie, C., Guinez, C., Lesage, J., Vieau, D., Eeckhoute, J., Gabory, A., Oger, F., Eberlé, D., Breton, C. Reduced PPARγ2 expression in adipose tissue of male rat offspring from obese dams is associated with epigenetic modifications.

Structural and functional changes of the pulmonary vasculature after hypoxia exposure in the neonatal period: a new swine model of pulmonary vascular disease.

Pulmonary vascular disease (PVD) represents an underestimated and increasing clinical burden not only in the neonatal period but also later in life, when exercise tolerance is decreased. Animal models performing long-term followup after a perinatal insult are lacking. This study aimed to develop and characterize a neonatal swine model with hypoxia-induced PVD during long-term followup after reexposure to normoxia and to investigate the exercise response in this model. Piglets were exposed to a normoxic ( n = 10) or hypoxic environment ( n = 9) for 4 wk. Neonatal hypoxia exposure resulted in pulmonary hypertension. Mean pulmonary artery pressure was elevated 1 day after reexposure to normoxia (30.2 ± 3.3 vs. 14.3 ± 0.9 mmHg) and remained significantly higher in the second week (32.8 ± 3.8 vs. 21.4 ± 1.2 mmHg), accompanied by decreased exercise tolerance. Exercise resulted in a trend toward an exaggerated increase of pulmonary artery pressure in hypoxia-exposed animals ( week 6, P = 0.086). Although pulmonary hypertension was transient, thickening of pulmonary arterioles was found at the end of followup. Furthermore, right ventricular dilation, lower right ventricular fractional area change ( week 8, 40.0 ± 2.7% vs. 29.5 ± 4.7%), and tricuspid annular plane systolic excursion ( week 8, 27.0 ± 2.5 vs. 22.9 ± 2.1 mm) persisted during followup. Male animals showed more severe PVD than female animals. In conclusion, we developed a neonatal swine model that allows examination of the long-term sequelae of damage to the developing neonatal lung, the course of the disease and the effect of therapy on long-term outcome. NEW & NOTEWORTHY The swine model of neonatal pulmonary vascular disease developed in the present study is the first that allows exercise testing and examination of long-term sequelae of a perinatal hypoxic insult, the course of the disease, and the effect of therapy on long-term outcome.

Maternal overweight is not an independent risk factor for increased birth weight, leptin and insulin in newborns of gestational diabetic women: observations from the prospective 'EaCH' cohort study.

BACKGROUND: Both gestational diabetes mellitus (GDM) as well as overweight/obesity during pregnancy are risk factors for detrimental anthropometric and hormonal neonatal outcomes, identified to 'program' adverse health predispositions later on. While overweight/obesity are major determinants of GDM, independent effects on critical birth outcomes remain unclear. Thus, the aim of the present study was to evaluate, in women with GDM, the relative/independent impact of overweight/obesity vs. altered glucose metabolism on newborn parameters. METHODS: The prospective observational 'Early CHARITÉ (EaCH)' cohort study primarily focuses on early developmental origins of unfavorable health outcomes through pre- and/or early postnatal exposure to a 'diabetogenic/adipogenic' environment. It includes 205 mother-child dyads, recruited between 2007 and 2010, from women with treated GDM and delivery at the Clinic of Obstetrics, Charité - Universitätsmedizin Berlin, Germany. Recruitment, therapy, metabolite/hormone analyses, and data evaluation were performed according to standardized guidelines and protocols. This report specifically aimed to identify maternal anthropometric and metabolic determinants of anthropometric and critical hormonal birth outcomes in 'EaCH'. RESULTS: Group comparisons, Spearman's correlations and unadjusted linear regression analyses initially confirmed that increased maternal prepregnancy body-mass-index (BMI) is a significant factor for elevated birth weight, cord-blood insulin and leptin (all P < 0.05). However, consideration of and adjustment for maternal glucose during late pregnancy showed that no maternal anthropometric parameter (weight, BMI, gestational weight gain) remained significant (all n.s.). In contrast, even after adjustment for maternal anthropometrics, third trimester glucose values (fasting and postprandial glucose at 32nd and 36th weeks' gestation, HbA1c in 3rd trimester and at delivery), were clearly positively associated with critical birth outcomes (all P < 0.05). CONCLUSIONS: Neither overweight/obesity nor gestational weight gain appear to be independent determinants of increased birth weight, insulin and leptin. Rather, 3rd trimester glycemia seems to be crucial for respective neonatal outcomes. Thus, gestational care and future research studies should greatly consider late pregnancy glucose in overweight/obese women with or without GDM, for evaluation of critical causes and interventional strategies against 'perinatal programming of diabesity' in the offspring.

Maternal prepregnancy BMI or weight and offspring's blood pressure: Systematic review.

Emerging evidence suggests that maternal prepregnancy body mass index or weight (MPBW) may be associated with offspring's blood pressure (BP). Therefore, we conducted a systematic review-following the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement-to assess and judge the evidence for an association between MPBW with offspring's later BP. Five data bases were searched without limits. Risk of bias was assessed using the "Tool to Assess Risk of Bias in Cohort Studies," and an evidence grade was allocated following the World Cancer Research Fund criteria. Of 2,011 publications retrieved, 16 studies (all cohort studies) were included in the systematic review; thereof, 5 studies (31%) were rated as good-quality studies. Overall, data from 63,959 participants were enclosed. Systolic BP was analysed in 15 (5 good quality), diastolic BP in 12 (3 good quality), and mean arterial pressure in 3 (no good quality) studies. Five good-quality studies of MPBW with offspring's systolic BP as the outcome and 1 good-quality study with offspring's diastolic BP as the outcome observed a significant association. However, after adding offspring's anthropometry variables to the statistical model, the effect attenuated in 4 studies with systolic BP to nonsignificance, the study with diastolic BP remained significant. No good-quality studies were found with respect to offspring's later mean arterial pressure. In conclusion, this systematic review found suggestive, but still limited, evidence for an association between MPBW with offspring's later BP. The available data suggest that the effect might be mainly mediated via offspring's anthropometry.

Perinatal programming by inflammation.

Since Levine and then Barker's seminal work mid to late last century demonstrating the importance of early life environment, intensive research has revealed the plasticity, vulnerability and resilience of the developing brain to environmental challenges. In particular, early exposure to infectious pathogens and inflammatory stimuli has a lasting impact on brain and behavior. These data establish clear effects on vulnerability to later disease and neuroinflammatory injury, cognitive function and emotionality, and even responses to pain and susceptibility to metabolic disorders. They also highlight the issues with defining rodent models of complex diseases like autism spectrum disorders and schizophrenia, as well as the complexity of experimental design, for instance when deciding the appropriate allocation of subjects to experimental groups when dealing with whole-litter manipulations in rodents. The studies presented in this special issue of Brain Behavior and Immunity are a collection of the very latest advances in the science of perinatal inflammation and its implications for perinatal programming of brain and behavior.

Plasma insulin levels in childhood are related to maternal factors--results of the Ulm Birth Cohort Study.

AIMS: The cardiovascular risk factor profile of a child as well as the development of body weight are influenced by genetic and childhood factors. Circulating insulin concentrations reflect the metabolic cardiovascular risk and may trigger weight gain. We aimed at identifying parental and childhood factors which may influence fasting plasma insulin concentrations in children. METHODS: The Ulm Birth Cohort study (UBCS) is a prospective birth cohort study. At baseline, birth characteristics, maternal pre-pregnancy body mass index (BMI) values as well as parental socioeconomic parameters were obtained. At the 8-yr follow-up examination, weights, heights, and fasting plasma insulin concentrations in n = 422 children and their parents were measured. Offspring of women with gestational diabetes mellitus were excluded from statistical analysis. RESULTS: Fasting plasma insulin concentrations of children were significantly correlated with maternal pre-pregnancy BMI values (r = 0.16) as well as with maternal (r = 0.26) but not with paternal fasting plasma insulin concentrations (r = 0.11) at the 8-yr follow-up examination. The risk for high fasting plasma insulin concentrations (≥75th internal percentile) was 2.30 (1.34-3.92) in children who also had high plasma insulin concentrations in umbilical cord blood compared to children having lower plasma insulin concentrations (<75th internal percentile) in umbilical cord blood. In addition, we observed that children with high fasting plasma insulin concentrations at the age of 8 had an altered BMI trajectory in childhood, characterized by higher BMI values from the age of 1 onwards, compared to children with lower insulin concentrations. CONCLUSION: Our observations support the hypothesis of perinatal programming of offspring insulin concentrations and BMI values by maternal pre-pregnancy BMI values.

Effects of sociocultural stressors on maternal responsivity and the infant behavioral and neuroendocrine response to stress in families of Mexican descent.

Maternal stress is consistently linked to alterations in maternal behavior and infant neurodevelopmental outcomes. As the Latino population grows in the U.S., it is increasingly important to understand how culturally relevant factors affect this relationship. This study aimed to address the role of sociocultural stressors on maternal sensitivity and markers of infant emotional regulation and the neuroendocrine response to stress in mother/infant dyads of Mexican descent. Pregnant women of Mexican descent (n = 115) were recruited during early pregnancy and followed until their infants were 6 months old. Mothers completed measures of sociocultural stressors (acculturative stress and discrimination) at pre and postnatal time points. At 6 months, dyads underwent the Still Face procedure. Mothers were observed for behaviors exhibiting maternal responsivity, while negative vocalizations were observed in infants. Salivary cortisol was also collected from infants. Maternal responsivity was a salient risk factor for alterations in infant emotional regulation and cortisol activity. Postnatal experiences of discrimination were also negatively associated with infant negative affect. This work highlights maternal responsivity and points to a potential role for experiences of discrimination in the response to stress in the mother/child dyad that may have consequences for the development of emotional regulation in infants of Mexican descent.

Maternal One-Carbon Nutrient Intake and Risk of Being Overweight or Obese in Their Offspring-A Transgenerational Prospective Cohort Study.

We aimed to investigate the associations between maternal intake of folate, vitamin B12, B6, B2, methionine, choline, phosphatidylcholine and betaine during the period surrounding pregnancy and offspring weight outcomes from birth to early adulthood. These associations were examined among 2454 mother-child pairs from the Nurses' Health Study II and Growing Up Today Study. Maternal energy-adjusted nutrient intakes were derived from food frequency questionnaires. Birth weight, body size at age 5 and repeated BMI measurements were considered. Overweight/obesity was defined according to the International Obesity Task Force (<18 years) and World Health Organization guidelines (18+ years). Among other estimands, we report relative risks (RRs) for offspring ever being overweight with corresponding 95% confidence intervals across quintiles of dietary factors, with the lowest quintile as the reference. In multivariate-adjusted models, higher maternal intakes of phosphatidylcholine were associated with a higher risk of offspring ever being overweight (RRQ5vsQ1 = 1.16 [1.01-1.33] p-trend: 0.003). The association was stronger among offspring born to mothers with high red meat intake (high red meat RRQ5vsQ1 = 1.50 [1.14-1.98], p-trend: 0.001; low red meat RRQ5vsQ1 = 1.05 [0.87-1.27], p-trend: 0.46; p-interaction = 0.13). Future studies confirming the association between a higher maternal phosphatidylcholine intake during pregnancy and offspring risk of being overweight or obese are needed.

Nutrition and adult neurogenesis in the hippocampus: Does what you eat help you remember?

Neurogenesis is a complex process by which neural progenitor cells (NPCs)/neural stem cells (NSCs) proliferate and differentiate into new neurons and other brain cells. In adulthood, the hippocampus is one of the areas with more neurogenesis activity, which is involved in the modulation of both emotional and cognitive hippocampal functions. This complex process is affected by many intrinsic and extrinsic factors, including nutrition. In this regard, preclinical studies performed in rats and mice demonstrate that high fats and/or sugars diets have a negative effect on adult hippocampal neurogenesis (AHN). In contrast, diets enriched with bioactive compounds, such as polyunsaturated fatty acids and polyphenols, as well as intermittent fasting or caloric restriction, can induce AHN. Interestingly, there is also growing evidence demonstrating that offspring AHN can be affected by maternal nutrition in the perinatal period. Therefore, nutritional interventions from early stages and throughout life are a promising perspective to alleviate neurodegenerative diseases by stimulating neurogenesis. The underlying mechanisms by which nutrients and dietary factors affect AHN are still being studied. Interestingly, recent evidence suggests that additional peripheral mediators may be involved. In this sense, the microbiota-gut-brain axis mediates bidirectional communication between the gut and the brain and could act as a link between nutritional factors and AHN. The aim of this mini-review is to summarize, the most recent findings related to the influence of nutrition and diet in the modulation of AHN. The importance of maternal nutrition in the AHN of the offspring and the role of the microbiota-gut-brain axis in the nutrition-neurogenesis relationship have also been included.