Offspring Metabolic Health Research Articles

Long-Term Endocrine and Metabolic Outcomes in Early Term Born Offspring: A Systematic Review and Meta-Analysis

Childhood endocrine and metabolic morbidity is a major global public health concern, with rising prevalence. Prematurity clearly impacts the long-term risk for such morbidity. We sought to systematically review the literature and evaluate whether early-term deliveries (370/7-386/7 weeks of gestation) impact the long-term endocrine and metabolic health of offspring up to the age of 18 years, as compared to offspring born at full term or later. This systematic review and meta-analysis was conducted according to the PRISMA guidelines and was registered in PROSPERO. We searched Medline, Embase, and relevant reference lists up to November 8th, 2020, including observational studies addressing the association. Two independent reviewers extracted data and assessed risk of bias. Pooled odds ratios (ORs) with their 95% confidence intervals (95% CIs) and heterogeneity were determined. Publication bias was assessed by Funnel plots with Eggers regression line and contours, and sensitivity analyses were performed using Baujat plots. Seven studies were included following a screen of over 5000 abstracts. Five studies were scored high quality according to the Newcastle-Ottawa Quality Assessment Scale. Early term delivery significantly increased the risk of total endocrine and metabolic morbidity in the offspring (OR=1.12, 95%CI=1.08, 1.17) as compared to full term delivery (Figure 1). The increased endocrine morbidity was mainly attributed to childhood diabetes (OR=1.14, 95%CI=1.09, 1.19) (Figure 2). Compared with full term born offspring, early term delivery poses a significant risk for long-term pediatric endocrine and metabolic morbidity. This association may be due to lack of full maturity of the hormonal axis in early term born children.

Maternal carbohydrate intake during pregnancy is associated with child peripubertal markers of metabolic health but not adiposity.

To examine the associations of trimester-specific maternal prenatal carbohydrate (CHO) intake with offspring adiposity and metabolic health during peripuberty. Prospective cohort study in which maternal dietary intake was collected via validated FFQ during each trimester. Offspring adiposity and metabolic biomarkers were evaluated at age 8-14 years. We used multivariable linear regression to examine associations between total energy-adjusted maternal CHO intake and offspring BMI z-score, skinfold thickness and metabolic syndrome risk z-score calculated as the average of waist circumference, fasting glucose, fasting C-peptide, TAG:HDL and systolic blood pressure + diastolic blood pressure/2. Mexico City, Mexico. 237 mother-child pairs in the Early Life Exposure in Mexico to Environmental Toxicants cohort. We found non-linear associations of maternal CHO intake during pregnancy with offspring metabolic health during peripuberty. After adjusting for maternal age, and child age, sex and pubertal status, children whose mothers were in the fourth v. first quartile of total CHO intake during the third trimester had 0·42 (95 % CI -0·01, 0·08) ng/ml lower C-peptide and 0·10 (95 % CI -0·02, 0·22) units lower C-peptide insulin resistance (CP-IR). We found similar magnitude and direction of association with respect to net CHO intake during the first trimester and offspring C-peptide and CP-IR. Maternal CHO intake during pregnancy was not associated with offspring adiposity. In this study of mother-child pairs in Mexico City, children born to women in the highest quartile of CHO intake during pregnancy had lowest C-peptide and CP-IR during peripuberty. Additional research is warranted to replicate and identify mechanisms.

Prenatal exposure to poly-/per-fluoroalkyl substances is associated with alteration of lipid profiles in cord-blood

IntroductionPoly-/per-fluoroalkyl substances (PFAS) are widespread environmental pollutants that may induce metabolic perturbations in humans, including particularly alterations in lipid profiles. Prenatal exposure to PFAS can cause lasting effects on offspring metabolic health, however, the underlying mechanisms are still unknown.ObjectivesThe goal of the study was to investigate the impact of prenatal PFAS exposure on the lipid profiles in cord blood.MethodsHerein, we combined determination of bile acids (BAs) and molecular lipids by liquid chromatography with ultra-high-resolution mass spectrometry, and separately quantified cord blood concentrations of sixteen PFAS in a cohort of Chinese infants (104 subjects) in a cross-sectional study. We then evaluated associations between PFAS concentration and lipidome using partial correlation network analysis, debiased sparse partial correlation, linear regression analysis and correlation analysis.ResultsPFAS levels showed significant associations with the lipid profiles; specifically, PFAS exposure was positively correlated with triacylgycerols (TG) and several bile acids. Importantly, exposure to perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), perfluorononanoic acid (PFNA) and perfluorohexane sulfonic acid (PFHxS) were associated with increased levels of TGs with saturated fatty acids while multiple classes of phospholipids were decreased. In addition, several free fatty acids showed significant positive correlations with PFOS.ConclusionsOur results indicated that prenatal exposure to PFAS mediated metabolic changes, which may explain the associations reported between PFAS exposure and metabolic health later in life.

The role of maternal diet on offspring hyperinsulinaemia and adiposity after birth: a systematic review of randomised controlled trials.

In utero diet may be directly related to the risk of fetal hyperinsulinaemia and offspring metabolic health. This review examines the relationship between maternal dietary exposures and sub-clinical fetal hyperinsulinaemia and neonatal adiposity. Articles were identified in MEDLINE, Web of Science, Cochrane Controlled Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature, SCOPUS, and SPORTDiscus (September 2019-March 2021) using the preferred reporting items for systematic reviews and meta-analyses guidelines. PROSPERO registration ID CRD42020146453. Studies were selected by two independent reviewers. Randomised controlled trials (RCT) involving a dietary intervention with pregnant women (healthy pregnancy, gestational diabetes mellitus and obesity) and reporting fetal cord-blood insulin, c-peptide, glucose or adiposity estimates were included. One author extracted all information on main study characteristics and outcomes. Risk of bias was assessed using the Cochrane Collaboration's bias risk assessment tool. A total of 733 articles were identified. Fourteen articles from 11 RCTs (3614 participants) were included. Studies reviewed showed no specific effect of maternal diet on neonatal cord blood insulin, c-peptide or glucose levels. Infants born to mothers who followed a low glycaemic load (GL) had lower skin fold thickness compared to controls. Interventions that provided individualised nutrition counselling to women with obesity or previous infant born > 4 kg were also associated with lower adiposity. The studies reviewed suggest that lifestyle-based dietary interventions to improve glycaemia (low GL) have a protective effect against excess adiposity. Future studies should incorporate multi-modal interventions with dietary counselling to support lifestyle changes throughout gestation and include assessments of maternal insulin resistance at recruitment.

Placental mTOR Signaling and Sexual Dimorphism in Metabolic Health across the Lifespan of Offspring

Robust evidence of fetal programming of adult disease has surfaced in the last several decades. Human and preclinical investigations of intrauterine insults report perturbations in placental nutrient sensing by the mechanistic target of rapamycin (mTOR). This review focuses on pregnancy complications associated with placental mTOR regulation, such as fetal growth restriction (FGR), fetal overgrowth, gestational diabetes mellitus (GDM), polycystic ovarian syndrome (PCOS), maternal nutrient restriction (MNR), preeclampsia (PE), maternal smoking, and related effects on offspring birthweight. The link between mTOR-associated birthweight outcomes and offspring metabolic health trajectory with a focus on sexual dimorphism are discussed. Both human physiology and animal models are summarized to facilitate in depth understanding. GDM, PCOS and fetal overgrowth are associated with increased placental mTOR, whereas FGR, MNR and maternal smoking are linked to decreased placental mTOR activity. Generally, birth weight is reduced in complications with decreased mTOR (i.e., FGR, MNR, maternal smoking) and higher with increased mTOR (GDM, PCOS). Offspring display obesity or a higher body mass index in childhood and adulthood, impaired glucose and insulin tolerance in adulthood, and deficiencies in pancreatic beta-cell mass and function compared to offspring from uncomplicated pregnancies. Defining causal players in the fetal programming of offspring metabolic health across the lifespan will aid in stopping the vicious cycle of obesity and type II diabetes.

Sex Differences in Early Programming by Maternal High Fat Diet Induced-Obesity and Fish Oil Supplementation in Mice.

Pre-pregnancy obesity is a contributing factor for impairments in offspring metabolic health. Interventional strategies during pregnancy are a potential approach to alleviate and/or prevent obesity and obesity related metabolic alterations in the offspring. Fish oil (FO), rich in omega-3 polyunsaturated fatty acids (n-3 PUFAs) exerts metabolic health benefits. However, the role of FO in early life remains still unknown. Hence, this study objective was to determine the effect of FO supplementation in mice from pre-pregnancy through lactation, and to study the post-natal metabolic health effects in gonadal fat and liver of offspring fed high fat (HF) diet with or without FO. Female C57BL6J mice aged 4–5 weeks were fed a HF (45% fat) diet supplemented with or without FO (30 g/kg of diet) and low fat (LF; 10% fat) pre-pregnancy through lactation. After weaning, offspring (male and female) from HF or FO dams either continued the same diet (HF-HF and FO-FO) or switched to the other diet (HF-FO and FO-HF) for 13 weeks, creating four groups of treatment, and LF-LF was used as a control group. Serum, gonadal fat and liver tissue were collected at termination for metabolic analyses. Offspring of both sexes fed HF with or without fish oil gained (p < 0.05) more weight post weaning, compared to LF-LF-fed mice. All the female offspring groups supplemented with FO had reduced body weight compared to the respective male groups. Further, FO-FO supplementation in both sexes (p < 0.05) improved glucose clearance and insulin sensitivity compared to HF-HF. All FO-FO fed mice had significantly reduced adipocyte size compared to HF-HF group in both male and females. Inflammation, measured by mRNA levels of monocyte chemoattractant protein 1 (Mcp1), was reduced (p < 0.05) with FO supplementation in both sexes in gonadal fat and in the liver. Markers of fatty acid synthesis, fatty acid synthase (Fasn) showed no sex specific differences in gonadal fat and liver of mice supplemented with HF. Female mice had lower liver triglycerides than male counterparts. Supplementation of FO in mice improved metabolic health of offspring by lowering markers of lipid synthesis and inflammation.

Effect of Gestational Diabetes Mellitus on the Growth, Development, and Stem Cells of Offspring

Abstract The effects of gestational diabetes mellitus (GDM) on offspring include macrosomia, hypoglycemia, respiratory distress syndrome, cardiovascular disease, neural and mental injury, etc. The effects of GDM on the health status of offspring are sustained although pregnancy has ended. It has been proposed that fetal reprogramming causes long-term consequences to metabolic health in offspring. An intrauterine high-glucose environment may lead to changes in the multi-differentiation proficiency of intracorporal stem cells, showing decreased proliferation and osteogenic ability, increased adipogenic ability, accelerated apoptosis, and occurrence of premature failure. This environment also reduces the mobilization of bone marrow stem cells, whereas it increases that of medullary cells. This results in pro-inflammatory conditions and sustained inflammation in the body, thereby increasing the risk of obesity, cardiovascular and neurological disorders, and metabolic abnormalities. Stem cells derived from the amniotic membrane, umbilical cord, or placenta may be a reliable predictor of the long-term effects of GDM on offspring. The levels of blood glucose during pregnancy should be effectively controlled to reduce harm to the neonate.

Long-Term Effects of Maternal Low-Protein Diet and Post-weaning High-Fat Feeding on Glucose Metabolism and Hypothalamic POMC Promoter Methylation in Offspring Mice.

Substantial evidence indicated that maternal malnutrition could increase the susceptibility to obesity, insulin resistance, and type 2 diabetes in adulthood. It is increasingly apparent that the brain, especially the hypothalamus, plays a critical role in glucose homeostasis. However, little information is known about the mechanisms linking maternal protein restriction combined with post-weaning high-fat (HF) feeding with altered expression of brain neurotransmitters, and investigations into the epigenetic modifications of hypothalamus in offspring have not been fully elucidated. Our objective was to explore the effects of maternal protein restriction combined with post-weaning HF feeding on glucose metabolism and hypothalamic POMC methylation in male offspring mice. C57/BL6 mice were fed on either low-protein (LP) or normal chow (NC) diet throughout gestation and lactation. Then, the male offspring were randomly weaned to either NC or high-fat (HF) diet until 32 weeks of age. Gene expressions and DNA methylation of hypothalamic proopiomelanocortin (POMC) and melanocortin receptor 4 (MC4R) were determined in male offspring. The results showed that birth weights and body weights at weaning were both significantly lower in male offspring mice of the dams fed with a LP diet. Maternal protein restriction combined with post-weaning high-fat feeding, predisposes higher body weight, persistent glucose intolerance (from weaning to 32 weeks of age), hyperinsulinemia, and hyperleptinemia in male offspring mice. POMC and MC4R expressions were significantly increased in offspring mice fed with maternal LP and postnatal high-fat diet (P < 0.05). Furthermore, maternal protein restriction combined with post-weaning high-fat feeding induced hypomethylation of POMC promoter in the hypothalamus (P < 0.05) and POMC-specific methylation (%) was negatively correlated with the glucose response to a glucose load in male offspring mice (r = −0.42, P = 0.039). In conclusion, maternal LP diet combined with post-weaning high-fat feeding predisposed the male offspring to impaired glucose metabolism and hypothalamic POMC hypomethylation. These findings can advance our thinking about hypothalamic POMC gene methylation between maternal LP diet combined with post-weaning high-fat feeding and metabolic health in offspring.

Exercise during Pregnancy: Developmental Programming Effects and Future Directions in Humans.

Epidemiological studies show that low birth weight is associated with mortality from cardiovascular disease in adulthood, indicating that chronic diseases could be influenced by hormonal or metabolic insults encountered in utero. This concept, now known as the Developmental Origins of Health and Disease hypothesis, postulates that the intrauterine environment may alter the structure and function of the organs of the fetus as well as the expression of genes that impart an increased vulnerability to chronic diseases later in life. Lifestyle interventions initiated during the prenatal period are crucial as there is the potential to attenuate progression towards chronic diseases. However, how lifestyle interventions such as physical activity directly affect human offspring metabolism and the potential mechanisms involved in regulating metabolic balance at the cellular level are not known. The purpose of this review is to highlight the effects of exercise during pregnancy on offspring metabolic health and emphasize gaps in the current human literature and suggestions for future research.

Gestational exposure to high fat diets and bisphenol A alters metabolic outcomes in dams and offspring, but produces hepatic steatosis only in dams

The prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing worldwide. Perinatal development is a critical window for altered, lifelong health trajectory, and evidence supports the role of perinatal programming in chronic metabolic diseases. To examine the impact of diet and bisphenol A (BPA) on the developmental trajectory of NAFLD in offspring, we exposed dams from pre-gestation through lactation to a human-relevant dose of oral BPA coupled with intake of high fat Western or Mediterranean-style diets. We assessed hepatic steatosis by quantifying hepatic triglycerides (TGs) and metabolic health by measuring body weight, relative organ weights, and serum hormone levels in dams and offspring at postnatal day 10 (PND10) and 10-months of age. In dams, consumption of the Western or Mediterranean diet increased hepatic TGs 1.7–2.4-fold, independent of BPA intake. Among offspring, both perinatal diet and BPA exposure had a greater impact on metabolic outcomes than on hepatic steatosis. At PND10, serum leptin levels were elevated 2.6–4.8-fold in pups exposed to the Mediterranean diet, with a trend for sex-specific effects on body and organ weights. At 10-months, sex-specific increases in organ weight and hormone levels were observed in mice perinatally exposed to Western + BPA or Mediterranean + BPA. These findings suggest lifestage-specific interaction of perinatal exposures to experimental diets and BPA on offspring metabolic health without effects on NAFLD later in life. Importantly, alterations in dam phenotype by diet and BPA exposure appear to impact offspring health trajectory, emphasizing the need to define dam diet in assessing effects of environmental exposures on offspring health.

Maternal Obesity: A Focus on Maternal Interventions to Improve Health of Offspring.

Maternal obesity has many implications for offspring health that persist throughout their lifespan that include obesity and cardiovascular complications. Several different factors contribute to obesity and they encompass interplay between genetics and environment. In the prenatal period, untreated obesity establishes a foundation for a myriad of symptoms and negative delivery experiences, including gestational hypertensive disorders, gestational diabetes, macrosomia, and labor complications. However, data across human and animal studies show promise that nutritional interventions and physical activity may rescue much of the adverse effects of obesity on offspring metabolic health. Further, these maternal interventions improve the health of the offspring by reducing weight gain, cardiovascular disorders, and improving glucose tolerance. Mechanisms from animal studies have also been proposed to elucidate the signaling pathways that regulate inflammation, lipid metabolism, and oxidative capacity of the tissue, ultimately providing potential specific courses of treatment. This review aims to pinpoint the risks of maternal obesity and provide plausible intervention strategies. We delve into recent research involving both animal and human studies with maternal interventions. With the increasing concerning of obesity rates witnessed in the United States, it is imperative to acknowledge the long-term effects posed on future generations and specifically modify maternal nutrition and care to mitigate these adverse outcomes.

Choline Supplementation in Obese Mouse Dams Alters Offspring DNA Methylation in a Time-Specific Manner

ObjectivesMaternal obesity has long-term influence on metabolic health of offspring, partly through an epigenetic mechanism. Choline is a methyl donor which provides methyl groups for epigenetic modification such as DNA methylation. In this study, we examined the effect of maternal choline supplementation (MCS) on DNA methylation of offspring born to high-fat (HF) fed obese mouse dams. MethodsC57BL/6J mice were fed either a 10% kcal normal fat (NF) or a 60% kcal HF diet with either 25 mM choline supplement or control drinking water from 4 weeks prior to mating until the end of gestation. The offspring were fed the HF diet for 6 weeks after weaning. We measured both global DNA methylation and site-specific methylation of several metabolic genes in the liver, visceral adipose tissue, and brain at both embryonic day E17.5 and after the post-weaning HF feeding. ResultsAt E17.5, HF-MCS led to higher global DNA methylation in both fetal liver and brain. Methylation of one of the CpGs in the promoter region of Srebp1f (a gene that regulates lipogenesis) was also upregulated in the fetal liver by HF-MCS, accordingly there was lower expression of this gene (p < 0.05). However, HF-MCS had opposite effects on global DNA methylation after 6 weeks of post weaning HF feeding than during the fetal period. At this time point, HF-MCS led to hypomethylation of liver and visceral adipose tissue (p < 0.05). Global DNA methylation of the brain was decreased by post-weaning HF feeding but was not affected by maternal HF or MCS (p < 0.01). ConclusionsIn conclusion, MCS during maternal obesity in the perinatal period influences offspring DNA methylation in a time-specific manner. The epigenetic programming effect of MCS needs to be evaluated in both short and long term in the offspring. Funding SourcesNIGMS.

Exercising for future generations

A placenta-to-fetus pathway transmits the benefits of maternal exercise on the metabolic health of offspring.

Placental superoxide dismutase 3 mediates benefits of maternal exercise on offspring health

Poor maternal diet increases the risk of obesity and type 2 diabetes in offspring, adding to the ever-increasing prevalence of these diseases. In contrast, we find that maternal exercise improves the metabolic health of offspring, and here, we demonstrate that this occurs through a vitamin D receptor-mediated increase in placental superoxide dismutase 3 (SOD3) expression and secretion. SOD3 activates an AMPK/TET signaling axis in fetal offspring liver, resulting in DNA demethylation at the promoters of glucose metabolic genes, enhancing liver function, and improving glucose tolerance. In humans, SOD3 is upregulated in serum and placenta from physically active pregnant women. The discovery of maternal exercise-induced cross talk between placenta-derived SOD3 and offspring liver provides a central mechanism for improved offspring metabolic health. These findings may lead to novel therapeutic approaches to limit the transmission of metabolic disease to the next generation.

Sex-specific effects of in vitro fertilization on adult metabolic outcomes and hepatic transcriptome and proteome in mouse.

Although in vitro fertilization (IVF) is associated with adverse perinatal outcomes, there is increasing concern about the long-term and sex-specific health implications. Augmenting our IVF mouse model to longitudinally investigate metabolic outcomes in offspring from optimal neonatal litter sizes, we found sex-specific metabolic outcomes in IVF offspring. IVF-conceived females had higher body weight and cholesterol levels compared to naturally conceived females, whereas IVF-conceived males had higher levels of triglycerides and insulin, and increased body fat composition. Through adult liver transcriptomics and proteomics, we identified sexually dimorphic dysregulation of the sterol regulatory element-binding protein (SREBP) pathways that are associated with the sex-specific phenotypes. We also found that global loss of DNA methylation in placenta was linked to higher cholesterol levels in IVF-conceived females. Our findings indicate that IVF procedures have long-lasting sex-specific effects on metabolic health of offspring and lay the foundation to utilize the placenta as a predictor of long-term outcomes.

Growth factors in the fetus and pre-adolescent offspring of hyperglycemic rats.

Background:Maternal hyperglycemia influences childhood metabolic syndrome, including obesity and hyperglycemia. We tested the hypothesis that the maternal hyperglycemia influences growth factors in the fetal and pre-adolescent offspring.Methods:Hyperglycemia was induced in pregnant rats on embryonic day (E)16 using streptozocin followed by implantation with insulin or placebo pellets at embryonic day 18 (E18). Fetuses at E20 and pre-adolescent pups at postnatal day 14 (P14) were studied: (1) normal untreated controls (CTL) at E20; (2) hyperglycemic placebo-treated (HPT) at E20; (3) hyperglycemic insulin-treated (HIT) at E20; (4) CTL at P14; and (5) HIT at P14. Fetal and pre-adolescent growth factors were determined.Results:Biomarkers of hypoxia were elevated in the HPT group at E20. This group did not survive to term. Maternal insulin improved fetal survival despite lower fetal body weight at E20, however, at normal birth (postnatal day 0 (P0)) and at P14, body weights and blood glucose were higher than CTL. These high levels correlated with aberrant growth factors. Maternal hyperglycemia influenced glucose-6-phosphate dehydrogenase, glucagon, insulin, interleukin-10, and leptin genes.Conclusions:The impact of maternal hyperglycemia on pre-adolescent glucose and body weight was not a consequence of maternal overnutrition. This suggests an independent link which may affect offspring metabolic health in later life.

Dysregulated appetitive leptin signaling in male rodent offspring from post-bariatric dams.

Bariatric surgery produces significant positive benefits to recipients such as resolution of various obesity-related comorbidities, including improved reproductive function. Females of childbearing age seek bariatric surgical remedies to improve their chance of successful pregnancy; however, limited knowledge exists on the impact of surgical weight loss to subsequently born offspring.We previously reported that circulating leptin levels were reduced in pregnant females having previously received vertical sleeve gastrectomy (VSG) in comparison to control dams having received Sham surgery. Furthermore, the levels of leptin receptors in the VSG placenta were also reduced in comparison to controls in. These data suggest there may be a significant difference in leptin signaling during pregnancy that may produce an altered developmental environment for the offspring.Here, we investigate the adult offspring of dams having received VSG or Sham-VSG prior to pregnancy. Endogenous fasting plasma leptin levels were not different between Sham and VSG offspring. Fasting leptin receptor mRNA in the medial basal hypothalamus (MBH) was elevated in VSG offspring in comparison to Sham. Intraperitoneal administration of exogenous leptin produced reductions in acute food intake in male Sham offspring, but did not reduce food intake at any time point measured in male VSG offspring. Using Western blot, we identified elevated pSTAT3 and pSTAT3/STAT3 ratios in the MBH of post-VSG offspring in comparison to controls. Using immunohistochemistry, we found an increased number of pSTAT positive cells in the arcuate nucleus in the Sham offspring in comparison to VSG. In contrast, within the paraventricular and ventromedial hypothalamic nuclei the VSG offspring had elevated numbers of pSTAT-positive cells in comparison to controls. Collectively, these data support our hypothesis that leptin signaling is dysregulated in VSG offspring and may be partially responsible for the long-term impact of maternal bariatric surgery on the metabolic health of offspring.

Intrauterine Exposure to Diabetic Milieu Does Not Induce Diabetes and Obesity in Male Adulthood in a Novel Rat Model.

Several studies show an association of maternal diabetes during pregnancy with adverse offspring metabolic health. Other studies, however, suggest that this effect might be biased by obesity, which is independently associated with offspring metabolic disease and often coexistent to maternal diabetes. We performed a prospective study in a rat model to test the hypothesis that the burden of a diabetic pregnancy without obesity deteriorates metabolic health in male offspring. We generated maternal type 2 diabetes before conception that persisted during pregnancy by knockdown of the insulin receptor in small hairpin RNA-expressing transgenic rats. Male WT (wild type) offspring were followed up until adulthood and metabolically challenged by high-fat diet. Blood glucose was measured continuously via a telemetry device. Glucose and insulin tolerance tests were performed, and body composition was analyzed. Weight gain and glucose levels during adolescence and adulthood were similar in male offspring of diabetic and control pregnancies. Body weight and fat mass after high-fat diet, as well as glucose and insulin tolerance tests, were unaltered between male adult offspring of both groups. Glycemic control consisting of up to 49 000 individual glucose measures was comparable between both groups. Intrauterine exposure to maternal hyperglycemia and hyperinsulinemia without obesity had no impact on male offspring metabolic health in our model. We conclude that the intrauterine exposure itself does not represent a mechanism for fetal programming of diabetes and obesity in our model. Other maternal metabolic parameters during pregnancy, such as obesity, might impact long-term offspring metabolic health.

418 Paternal Programming of Offspring Health

Abstract There is now a significant body of human and animal model data identifying common associations between perturbed development during gestation, disproportionate fetal growth and poor adult cardiovascular and metabolic health. Typically, these studies have focused on the impact of poor maternal health on offspring development and well-being. However, a growing evidence base now indicates that sub-optimal paternal factors (such as diet) can also program adult offspring ill-health. While the link between paternal health and offspring well-being is becoming established, attention is being focused on defining the underlying mechanism(s). Here, the father may influence post-fertilization development through two main pathways, the integrity and status of the sperm genome (including epigenome) and through components of the seminal plasma. We have used a mouse model of paternal low protein diet to study the impact sub-optimal nutrition has on the quality and epigenetic status of the sperm, embryonic development and fetal growth. We have also used our model to study the relative seminal plasma and sperm contributions to adult offspring cardiovascular and metabolic health. Our studied highlight the role of a father’s diet at the time of conception for the development and well-being of his offspring.

Redox Mechanism for the Beneficial Effect of Maternal Exercise to Improve OffSpring Metabolic Health

Redox Mechanism for the Beneficial Effect of Maternal Exercise to Improve OffSpring Metabolic Health