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Introduction: Non-diabetic individuals with type II diabetic parents are more susceptible to develop Diabetes. Visfatin; an adipocytokine and an enzyme is linked with glucose metabolism and affected by obesity. It works like insulin in the human body. It serves as a key enzyme in nicotinamide adenine dinucleotide biosynthesis and plays a pivotal role in glucose mediated insulin secretion. Aims and Objectives: In this study we aimed to determine and compare serum visfatin levels, insulin resistance (HOMA-IR) and beta cell function (HOMA-%B) of type II diabetic patients and non-diabetic adult offspring of type II diabetic parents with that of non-diabetic adult offspring of non-diabetic parents. Material and methods It was a cross-sectional comparative study conducted at Diabetes clinic of Lahore General Hospital (LGH) and department of Physiology, Post Graduate Medical Institute (PGMI), Lahore in 2018. The study groups included thirty type II diabetic subjects (group III) and forty non-diabetic adult offspring of type II diabetic parents (group II). Forty non-diabetic adult offspring of non-diabetic parents served as controls (group I). The subjects were of thirty to fifty years of age. Blood pressure, BMI and waist circumference of every subject was measured. Fasting blood samples of the subjects were analyzed for serum insulin, glucose and visfatin. Insulin resistance (HOMA-IR), insulin sensitivity (HOMA-%S) and beta cell function (HOMA-%β) were also calculated. Results Type II diabetics (group III) had significantly higher serum visfatin, HOMA-IR, and lower HOMA-%S as compared to the controls (group I). No significant difference was found between HOMA-%B of group III and controls. On the contrary, non-diabetic adult offspring of type II diabetic parents (group II) had significantly lower serum visfatin and HOMA-%S while HOMA-%β, HOMA-IR was significantly higher in comparison to the control group (group I). Conclusion Visfatin production seems suppressed in non-diabetic individuals with type II diabetic parents probably due to hyperinsulinemia. Moreover, it has a little role in insulin secretion in these individuals as reflected by their higher HOMA-%B index. However, visfatin’s upregulation in chronic hyperglycemia is indicative of its restorative role in the declined beta-cell function in type II diabetics.

Objective:There is growing evidence that exposure to trauma prior to conception can affect offspring. The authors have reported that adult offspring of Holocaust survivors showed lower methylation ...

Exposure to different stressors in utero is linked to adult diseases such as obesity and hypertension. In this study, the impact of prenatal infection (PNI) on adult body weight and cardiovascular function was evaluated using a naturally occurring rodent pathogen, Mycoplasma pulmonis (MP). Pregnant Sprague-Dawley rats were infected with MP on gestational day 14 and gave birth naturally. Adult PNI offspring weighed more than controls, but resting mean arterial pressure (MAP) was unchanged. Subcutaneous injection of angiotensin II (10 μg/kg) elicited a rise in MAP that was greater in both male and female PNI offspring compared with controls ( P < 0.03). The accompanying reflex bradycardia was similar to the controls, suggesting that PNI induced baroreflex dysfunction. Subcutaneous nicotine administration, a potent cardiorespiratory stimulus, also elicited a transient rise in MAP that was generally greater in the PNI group, but the change in MAP from baseline was only significant in the PNI females compared with controls ( P < 0.03). Elevated body weight and cardiovascular reactivity in the PNI offspring was associated with an increase in the ratio of hypothalamic corticotrophin-releasing hormone receptors type 1 to type 2 gene expression in both sexes compared with controls. These findings support previous studies demonstrating that PNI induces alterations in cardiovascular function and body weight. Yet, unlike previous studies utilizing other models of PNI (e.g., endotoxin), MP PNI did not induce resting hypertension. Thus, our study provides a foundation for future studies evaluating the cardiovascular risks of offspring exposed to microbial challenges in utero.

Objective: Posttraumatic stress disorder (PTSD) has been associated with lower circulating cortisol levels in specific subgroups, which have also been found in the offspring of people with PTSD. The analysis of hair cortisol concentrations (HCC) is a recent methodology which is used to assess long-term systemic cortisol levels. We aimed to study veterans with war-related lifetime PTSD and their respective offspring with regards to HCC. We also studied the influence of lifetime major depressive disorder (MDD), war experiences, and childhood adversities on HCC in these groups. Methods: 31 male veterans with PTSD and 28 without PTSD and 69 adult offspring were studied. HCC were quantified by liquid chromatography tandem-mass spectrometry. Results: No differences in HCC were found between veterans with and without PTSD, or between their respective offspring. Veterans without MDD showed a positive association between total war exposure and HCC. Veterans reporting more frequent childhood physical abuse had lower HCC. Veterans-with-PTSD's offspring with MDD had increased HCC compared to offspring without MDD. Offspring's exposure to more frequent childhood physical abuse was negatively associated with HCC in those without MDD. Conclusion: HCC did not appear to constitute a marker of intergenerational heritage of war-related PTSD, except in the case of veteranswith-PTSD's offspring with MDD. Our data suggest that HCC is a marker of adult reported childhood physical abuse. The second author (EFCvR) has been supported by an Erasmus MC research fellowship, and the Netherlands Brain Foundation (grant number F2011(1)-12), and is currently supported by a a Vidi grant from the Netherlands Organization of Scientific Research NWO (grant number: 91716453). This work was partially supported by the Associação dos Amigos do Serviço de Endocrinologia do Hospital de São João.

Exercise has profound effects on cardiovascular function and metabolism in both physiological and pathophysiological states. Our previous studies demonstrated that maternal gestational hypertension (MGHT) induces hypertensive response sensitization (HTRS) elicited by post-weaning high fat diet (HFD) in male offspring. The present study tested whether voluntary exercise would protect against MGHT-induced HTRS in HFD fed male offspring. Male offspring from both normotensive (NT) and MGHT dams were given access to either “blocked” (sedentary offspring) or functional running (exercised offspring) wheels for 10 weeks during normal fat diet (NFD) or HFD feeding. HFD feeding significantly increased resting blood pressure (BP) in sedentary offspring of both NT (112.3±0.7 to 119.9±1.2 mmHg, p0.05). Voluntary exercise did not alter BP in NFD fed offspring and HFD fed offspring of NT dams, but it attenuated BP in HFD fed offspring of MGHT dams (129.6±1.0 to 121.1±0.8 mmHg, p

Objective The purpose of this study was to investigate whether obstetric and perinatal socio-behavioral characteristics at the time of pregnancy predict obesity phenotypes of adult offspring. Methods The Jerusalem Perinatal Study was conducted among 17,003 deliveries during 1974 to 1976. Follow-up studies were conducted during 2007 to 2009 and 2017 to 2019 among 1,440 offspring undergoing examinations. Offspring were classified into four phenotypes according to obesity and metabolic status: metabolically healthy normal weight (MHNW, reference group), unhealthy normal weight, healthy obesity (MHO), and unhealthy obesity (MUO). Regression models were carried out to identify perinatal predictors for risk phenotypes at age 30 to 35 years, emphasizing the differentiation between socio-behavioral and obstetric features. Results A total of 15.7% of participants were classified as MUO, and 5.4% were classified as MHO. Low socioeconomic status was associated with both obesity phenotypes (e.g., odds ratio [OR]MHO/MHNW = 2.98, p Conclusions Perinatal socio-behavioral characteristics are associated with adult obesity phenotypes. The findings point to possible mechanisms underlying the development of obesity in young adults and, thus, contribute toward identifying high-risk groups that would mostly benefit from obesity risk-reduction interventions.

Although maternal high-fructose intake induces cardiometabolic syndrome in adult offspring, whether it induces hypertension in successive multiple generations has not yet been studied. We hypothesized that maternal high-fructose intake induces multigenerational activation of the renin-angiotensin-aldosterone system. Pregnant mice were offered 20% fructose in drinking water, of which subsequent first to fourth generation offspring were raised without being offered fructose. Blood pressure was measured via the tail-cuff method, mRNA expression was determined using the quantitative polymerase chain reaction, and fibrosis was evaluated using trichrome staining. Maternal high-fructose intake statistically significantly increased blood pressure in the first and second, but not the third and fourth, generation offspring as compared to the control group, with maximal increases in serum renin, angiotensin II, and aldosterone in the third generation offspring. It increased the mRNA expression of renin-angiotensin-aldosterone system genes as well as the expression of renin in the kidneys in the first to third generation offspring, with the exception of the vasodilatory Mas1 gene, the mRNA expression of which was the lowest in the second generation offspring. Moreover, it maximally increased fibrosis and the mRNA expression of inflammatory cytokines in the second generation offspring and increased the mRNA expression of oxidative factors in the first to third generation offspring, but maximally decreased the mRNA expression of antioxidant-encoding Sod1 in the second generation offspring. Maternal high-fructose intake induces multigenerational activation of renin-angiotensin-aldosterone system, and the results of this study implicate that it epigenetically induces cardiometabolic syndrome in multiple generations of offspring.

Background: Prenatal caffeine adversely affects learning and memory in adult offspring, whereas its administration to adolescent humans improves consolidation of long-term memory. The effects of po...

Background: Waterpipe tobacco smoke (WTS) is a popular form of tobacco consumption. Prenatal exposure to cigarette smoke altered kidney function and oxidative stress balance in offspring. H...

INTRODUCTION Early detection is critical in the prevention of cardiovascular disease (CVD). An at-risk population for cardiac disease-and conveniently approachable in terms of timing-is cardiac patients' offspring, at the moment when the parent is hospitalized for his or her own cardiac event. Based on the theoretical underpinning of life turning points, defined as perceived life course-changing events, we suggest that adult children would view the parent's cardiac event as a significant life turning point and that this understanding would motivate them to learn about CVD and to change their lifestyles accordingly. The current study's main goal was therefore to assess the baseline level and change over time in the adult offspring's knowledge of cardiac risk factors and cardiac health-promoting behaviors. METHOD In a prospective design, 69 Israeli adult offspring of individuals newly diagnosed with an acute coronary event were approached and interviewed at 3 time points (on average 17 days, 55 days, and 125 days after the parent's hospitalization). RESULTS Contrary to our assumption, no significant change over time was detected among the adult children with regard to body mass index, physical activity, eating behaviors, or smoking. In fact, over time, they seemed to know less about CVD risk factors than they did originally. CONCLUSION Adult children of cardiac patients seem to be reluctant to spontaneously engage in health-promoting behaviors. The option of approaching them, in a primary preventive act, as early as during a parent's hospitalization should be further investigated. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Parental health influences embryonic development and susceptibility to disease in the offspring. We investigated whether maternal voluntary running during gestation could protect the offspring from the adverse effects of maternal or paternal high-fat diet (HF) in mice. We performed transcriptomic and whole-genome DNA methylation analyses in female offspring skeletal muscle and targeted DNA methylation analysis of the peroxisome proliferator-activated receptor-γ coactivator-1α (Pgc-1α) promoter in both male and female adult offspring. Maternal HF resulted in impaired metabolic homeostasis in male offspring at 9 mo of age, whereas both male and female offspring were negatively impacted by paternal HF. Maternal exercise during gestation completely mitigated these metabolic impairments. Female adult offspring from obese male or female parent had skeletal muscle transcriptional profiles enriched in genes regulating inflammation and immune responses, whereas maternal exercise resulted in a transcriptional profile similar to offspring from normal chow (NC)-fed parents. Maternal HF, but not paternal HF, resulted in hypermethylation of the Pgc-1α promoter at CpG-260, which was abolished by maternal exercise. These findings demonstrate the negative consequences of maternal and paternal HF for the offspring’s metabolic outcomes later in life possibly through different epigenetic mechanisms, and maternal exercise during gestation mitigates the negative consequences. NEW & NOTEWORTHY Maternal or paternal obesity causes metabolic impairment in adult offspring in mice. Maternal exercise during gestation can completely mitigate metabolic impairment. Maternal obesity, but not paternal obesity, results in hypermethylation of the Pgc-1α promoter at CpG-260, which can be abolished by maternal exercise.

Background High dietary sodium intake can induce endothelial stiffness even without changes in blood pressure. Objectives To evaluate the effects of exercise training and chronic intake of sodium chloride solution on aortic morphology of male offspring of rat dams who consumed flaxseed during lactation. Methods Female rats were fed with a control diet or a flaxseed diet during lactation. At weaning, two male offspring of each rat dam were allocated into eight groups for 180 days: four groups received a control diet e four received a flaxseed diet, with /without exercise and with/without NaCl solution supply. Aorta was collected for histomorphometric analysis. The one-way analysis of variance was used and P value < 0.05 was considered statistically significant. Results The chronic use of 1% NaCl solution led to changes in aortic histoarchitecture in the control group: increase in aortic intima-media thickness (10,4%, p

Background and objective Maternal high-fat diet (HFD) has been shown to modulate vascular function and remodeling in adult offspring. Atherosclerotic vascular calcification is closely associated with the onset of cardiovascular event. We therefore investigated the impact of maternal HFD on calcification of atherogenic plaques. Methods and results Eight-week-old female apo-E−/− mice (C57BL/6) were fed an HFD or a normal diet (ND) one week prior to mating, and the diet was continued throughout gestation and lactation. Offspring of both groups were fed a high-cholesterol diet (HCD) from 8 weeks of age. Ex vivo osteogenic activity of aortic root and aortic arch was analyzed using in vivo imaging system (IVIS) with OsteoSense 680. Sixteen-week-old male offspring of HFD-fed dams (O-HFD) showed a 1.4-fold increase in fluorescent intensity compared with those of ND-fed dams (O-ND) (p Conclusion Our findings demonstrate that maternal HFD accelerates the development of atherogenic calcification independent of plaque size. In vitro transformation to osteochondrocytic-like cells is enhanced in VSMCs from offspring of HFD-fed dams. Inhibition of VSMCs skewing toward osteochondrocytic-like cells could be a potential therapeutic target for preventing the development of atherosclerotic vascular calcification. Funding Acknowledgement Type of funding source: None

Background and objective Maternal high-fat diet (HFD) has been shown to modulate vascular function and remodeling in adult offspring. Here, we investigated the impact of maternal HFD on abdominal aortic aneurysm (AAA) formation. Methods and results Eight-week-old female wild-type mice (C57BL/6) were fed a HFD or normal diet (ND) one week prior to mating, and the diet was continued throughout gestation and lactation. In eight-week-old male offspring, AAA was induced with the application of 0.5 M calcium chloride (CaCl2) on the infrarenal aorta. Offspring of HFD-fed dams (O-HFD) showed a significant increase in maximum outer diameter of AAA at 1, 4 and 8 weeks after surgery compared with offspring of ND-fed dams (O-ND). The lengths of outer circumference assessed by histological analysis were increased in O-HFD (p Conclusion Our findings demonstrate that maternal HFD accelerates CaCl2-induced AAA expansion, accompanied by the exaggerated accumulation of osteoclast-like macrophages and augmented activity of MMPs. Inhibition of macrophages skewing toward osteoclast-like cells could be a potential therapeutic target for preventing AAA development. Funding Acknowledgement Type of funding source: None

Kidney disease and hypertension both have attained the status of a global pandemic. Altered renal programming resulting in kidney disease and hypertension can begin in utero. Maternal suboptimal nutrition and oxidative stress have important implications in renal programming, while specific antioxidant nutrient supplementations may serve as reprogramming strategies to prevent kidney disease and hypertension of developmental origins. This review aims to summarize current knowledge on the interplay of maternal nutrition and oxidative stress in response to early-life insults and its impact on developmental programming of kidney disease and hypertension, covering two aspects. Firstly, we present the evidence from animal models supporting the implication of oxidative stress on adult kidney disease and hypertension programmed by suboptimal maternal nutrition. In the second part, we document data on specific antioxidant nutrients as reprogramming strategies to protect adult offspring against kidney disease and hypertension from developmental origins. Research into the prevention of kidney disease and hypertension that begin early in life will have profound implications for future health.

Background: In an effort to decrease the rates of smoking conventional tobacco cigarettes, electronic cigarettes (e-cigarettes) have been proposed as an effective smoking cessation tool. However, little is known about their toxicological impacts. This is concerning given that e-cigarette use is perceived as less harmful than conventional tobacco cigarettes during pregnancy for both the mother and fetus. Objective: The goal of this study was to test the neurodevelopmental consequences of maternal e-cigarette use on adult offspring behavior and neuroimmune outcomes. Methods: Pregnant female CD-1 mice were randomly assigned to one of three treatment groups (n=8–10 per group) and exposed daily to either filtered air, propylene glycol and vegetable glycerol (50:50 PG/VG vehicle), or to PG/VG with 16mg/mL nicotine (+Nic). Whole-body exposures were carried out for 3 h/d, 7 d/week, from gestational day (GD)0.5 until GD17.5. Adult male and female offspring (8 weeks old) were assessed across a battery of behavioral assessments followed by region-specific quantification of brain cytokines using multiplex immunoassays. Results: Adult offspring of both sexes exposed to +Nic exhibited elevated locomotor activity in the elevated plus maze and altered stress-coping strategies in the forced swim task. Moreover, male and female offspring exposed to PG/VG with and without nicotine had a 5.2% lower object discrimination score in the novel object recognition task. In addition to differences in offspring behavior, maternal e-cigarette exposure with nicotine led to a reduction in interleukin (IL)-4 and interferon-gamma (IFNγ) in the diencephalon, as well as lower levels of hippocampal IFNγ (females only). E-cigarette exposure without nicotine resulted in a 2-fold increase of IL-6 in the cerebellum. Discussion: These findings support previous adverse findings of e-cigarette exposure on neurodevelopment in a mouse model and provide substantial evidence of persistent adverse behavioral and neuroimmunological consequences to adult offspring following maternal e-cigarette exposure during pregnancy. https://doi.org/10.1289/EHP6067

Exposure to predation risk can induce a fearful baseline state, as well as fear reactions toward novel situations (i.e., neophobia). Some research indicates that risk exposure during sensitive periods makes adults more prone to acquiring long-term fearful phenotypes. However, chronic risk can also lead to ignoring threats in order to maintain other activities. We sought to assess how a relatively long period of low risk, experienced either early in life or by the previous generation, influences fear behaviour acquired from a short period of high risk as adults. We used fathead minnows as study subjects and simulated predation risk with repeated exposures to conspecific chemical alarm cues. The period of high risk experienced by adults induced typical fear behaviour (baseline freezing and neophobia), whereas the early-life low-risk period 1 year prior caused only a reduction in baseline foraging. We found no evidence that the early-life risk significantly altered the fear acquired from the adult-risk period. However, in a second experiment, a low-risk period during the parental generation interacted with a high-risk period experienced by the adult offspring. The combination of both risk periods heightened baseline freezing despite parental risk having little effect independently. Hence, our study provides evidence that parental risk exposure can lead to an additive intergenerational effect on fear acquisition in minnows.

Purpose: Advanced glycation end products (AGEs) are a heterogeneous group of highly oxidant compounds which can potentiate microvascular and macrovascular complications through the formation of irreversible cross-links between molecules in the basal membrane and also by engaging the receptor for AGEs (RAGE). Soluble receptor for AGEs (sRAGE) is suggested to have a protective role neutralizing the toxic action of AGEs. We aimed to investigate differences in plasma levels of sRAGE alongside with classic cardiovascular risk factors between offspring of patients with early onset of coronary heart disease (CHD) and healthy controls. Materials and methods: In a cross-sectional design, we examined 114 adult offspring of patients with premature CHD and 194 controls. Concentrations of soluble RAGE were quantified by ELISA methods. Aortic PWV was measured using Sphygmocor device. Multivariate logistic regressions were used to compare differences between the offspring and controls. Results: In the offspring group there were more men (p = 0.023), both groups had similar age (28.5 vs. 28.9 years; p = 0.51). After adjustment for covariates, we observed significantly higher aPWV (6.17 vs. 5.82 m s−1; p = 0.001) and lower sRAGE (1308.11 vs. 1475.59; p = 0.009) in the offspring group compared to controls. The significant determinants of the intergroup difference were sRAGE (p = 0.0017), aPWV (p = 0.011) and current smoking (p = 0.0053). Conclusion: Offspring of patients with early onset of CHD compared to age-matched healthy controls had significantly lower sRAGE levels suggesting a shift in the oxidative balance between stressors and defence mechanisms that may influence a higher cardiovascular risk in the future. The measurement of sRAGE might be a valuable predictor for more precise stratification of cardiovascular risk.

Background Results from observational and experimental studies indicate that exposure to air pollutants during gestation reduces birth weight, whereas little is known on potential cardiometabolic consequences for the offspring at adulthood. Objectives Our aim was to evaluate the long-term effects of gestational exposure to diesel engine exhaust (DE) on adult offspring phenotype in a rabbit model. Methods The protocol was designed to mimic human exposure in large European cities. Females rabbits were exposed to diluted (1 mg/m3) DE (exposed, n = 9) or clean air (controls, n = 7), from 3 days after mating, 2 h/d and 5 d/wk in a nose-only inhalation system throughout gestation (gestation days 3–27). After birth and weaning, 72 offspring (47 exposed and 25 controls) were raised until adulthood (7.5 months) to evaluate their cardio-metabolic status, including the monitoring of body weight and food intake, fasting biochemistry, body composition (iDXA), cardiovascular parameters and glucose tolerance. After a metabolic challenge (high fat diet in males and gestation in females), animals were euthanized for postmortem phenotyping. Results Sex-specific responses to maternal exposure were observed in adult offspring. Age-related increases in blood pressure (p = 0.058), glycaemia (p = 0.029), and perirenal fat mass (p = 0.026) as well as reductions in HDL-cholesterol (p = 0.025) and fat-to-body weight ratio (p = 0.011) were observed in exposed males, suggesting a metabolic syndrome. Almost only trends were observed in exposed females with higher triglycerides and decreased bone density compared to control females. Metabolic challenges triggered or amplified some biological responses, especially in females. Conclusions In utero exposure to air pollution predisposed rabbit offspring to cardiometabolic disorders in a sex-specific manner.

Gestational diabetes mellitus (GDM) is one form of diabetes affect approximately 7 % of pregnancies. Diabetic peripheral neuropathy (DPN) is a common complication of diabetes that is associated with loss of nerve fibers, myelin abnormalities and significant decrease in the expression of myelin basic protein (MBP) in peripheral nerves. This study was done to determine the effect of induced diabetes during pregnancy on sciatic nerve in adult rat offspring. In this study, wistar rats' dams were allocated to control and diabetic groups. Diabetic rats were received 40 mg/kg/body weight of streptozotocin (STZ) on the first day of gestation. Six offspring of each group were randomly selected on 12 weeks postnatal and histopathological changes in their nerve tissue were examined through H&E staining and transmission electron microscopy. Furthermore, the expression of MBP in sciatic nerve was examined by immunohistochemistry. We found that the myelinated fiber number of sciatic nerve in offspring of diabetic rats was reduced compared to the controls, but this difference was not significant. The average thickness of the myelin sheath of sciatic nerve fibers in the control and GDM was 97.1±0.1and 94.1±0.2 µm, respectively that the difference was not statistically significant. The expression of MBP protein in the myelin sheath of both groups was similar. TEM results showed that myelin sheath of diabetic offspring had not any changes compared to control. Atrophy of axons and schwannocytus (Schwann cells) alterations were not observed in diabetic offspring. Induction of diabetes during pregnancy reduced the number of nerve fibers and thickness of the myelin sheath. But it has no effect on MBP expression and schwannocytus morphology.

Background Maternal high-fat diet (HFD) has been shown to promote the development of insulin resistance (IR) in adult offspring; however, the underlying mechanisms remain unclear. Approach and results Eight-week-old female wild-type mice (C57BL/6) were fed a HFD or normal diet (ND) one week prior to mating, and received during pregnancy and lactation. Eight-week-old male offspring of both groups were fed a HFD for 8 weeks. Offspring of HFD-fed dams (O-HFD) showed significantly enhanced IR compared with offspring of ND-fed dams (O-ND). There was no difference in body weight, epidydimal white adipose tissue (eWAT) weight, and cumulative caloric intake between the 2 groups. However, eWAT adipocyte size was significantly increased in O-HFD, accompanied by the abundant crown-like structures. Flow cytometric analysis revealed an increased percentage of M1, but not M2, macrophages. Serum and eWAT concentrations of IL-1β, but not TNF-α, were significantly higher in O-HFD than O-ND (3.7-fold and 2.0-fold, respectively, P Conclusions Our findings demonstrate that maternal HFD exaggerates diet-induced insulin resistance in adult offspring by enhancing pyroptosis through augmented GSDM-D-mediated pore formation.

Background and objective Maternal high-fat diet (HFD) has been shown to modulate vascular function and remodeling in adult offspring. Here, we investigated the impact of maternal HFD on abdominal aortic aneurysm (AAA) formation. Methods and results Eight-week-old female wild-type mice (C57BL/6) were fed a HFD or normal diet (ND) one week prior to mating and received during pregnancy and lactation. In eight-week-old offspring of both genders, AAA was induced with the application of 0.5M calcium chloride (CaCl2) on the infrarenal aorta. Male offspring of HFD-fed dams (O-HFD) showed a significant increase in maximum outer diameter of AAA at 1, 4 and 8 weeks after surgery compared with offspring of ND-fed dams (O-ND) (P Conclusion Our findings demonstrate that maternal HFD accelerates CaCl2-induced AAA expansion, accompanied by the exaggerated accumulation of osteoclast-like macrophages and augmented activity of MMPs. Inhibition of macrophages skewing toward osteoclast-like cells could be a potential therapeutic target for preventing AAA development.

Obesity is strongly associated with cardiomyopathy and heart failure. We examined the impact of paternal and maternal obesity on systolic and diastolic function in male adult offspring. The following groups were studied: 1) offspring fed normal diet (ND) born from ND parents (ND-F1-ND, n=5); 2) offspring fed high fat diet (HFD) born from ND parents (HFD-F1-ND, n=6); 3) offspring fed ND born from HFD parents (ND-F1-HFD, n=7); and 4) offspring fed HFD born from HFD parents (HFD-F1-HFD, n=7). Parents were fed HFD or ND from weaning until the end of lactation, while the offspring were placed on ND or HFD from weaning until the end of experiments. Body weight, fat and lean mass, measured using EchoMRI4-in-1 System, were measured weekly. Cardiac function including ejection fraction (EF), isovolumetric relaxation time (IVRT), late filling velocity (A’), E and E’ early filling velocities were determined at 22 weeks of age using long and short axis left ventricle dimensions, pulse wave and tissue Doppler (VisualSonics 30 MHZ transducer, VEVO3100®). Compared to lean control ND-F1-ND mice, ND-F1-HFD mice had similar body weight (28.9±1.0 vs. 27.9±0.4 g) but higher fat mass (4.5±0.9 vs. 3.0±0.3 g) and lower lean mass (22.9±0.4 vs. 24.6±0.3 g). Both groups of mice fed HFD after weaning were heavier than offspring fed ND. However, HFD-F1-HFD mice were heavier than HFD-F1-ND mice (47.3±0.8 vs. 42.5±1.9 g) due to greater fat mass (19.4±0.6 vs. 15.7±1.6 g) and lean mass (28.3±0.6 vs. 26.9 vs. 0.3 g). Despite no major differences in ejection fraction among all 4 groups, mice fed HFD or born from parents fed HFD exhibited diastolic dysfunction; worse indicators of diastolic function were observed in mice from HFD parents as indicated by increased IVRT (30.4±1.8, 25.0±1.8, 22.1±2.0 vs. 21.4±0.9 ms) and E/E’ ratio (36.6±3.6, 32.3±1.8, 31.8±1.2 vs. 27.9±2.5) and reduced E’/A’ ratio (0.9±0.1, 0.7±0.1, 1.5±0.2 vs. 1.4±0.1) for HFD-F1-HFD, ND-F1-HFD, HFD-F1-ND and ND-F1-ND, respectively. These results indicate that diet-induced parental obesity is associated with diastolic dysfunction and preserved EF in the offspring, which is exacerbated by HFD-induced obesity. (NHLBI-PO1HL51971, NIGMS P20GM104357 and U54GM115428)

Creatine plays a crucial role in developing the brain, so much that its genetic deficiency results in mental dysfunction and cognitive impairments. Moreover, creatine supplementation is currently under investigation as a preventive measure to protect the fetus against oxidative stress during difficult pregnancies. Although creatine use is considered safe, posing minimal risk to clinical health, we found an alteration in morpho-functional maturation of neurons when male rats were exposed to creatine loads during brain development. In particular, increased excitability and enhanced long-term potentiation (LTP) were observed in the hippocampal pyramidal neurons of weaning pups. Since these effects were observed a long time after creatine treatment had been terminated, long-lasting modifications persisting into adulthood were hypothesized. Such modifications were investigated in the present study using morphological, electrophysiological, and calcium imaging techniques applied to hippocampal Cornu Ammonis 1 (CA1) neurons of adult rats born from dams supplemented with creatine. When compared to age-matched controls, the treated adult offspring were found to retain enhanced neuron excitability and an improved LTP, the best-documented neuronal substrate for memory formation. While translating data from rats to humans does have limitations, our findings suggest that prenatal creatine supplementation could have positive effects on adult cognitive abilities.

Exposure to maternal diabetes during pregnancy results in diabetes in offspring, but its underlying mechanisms are unclear. Here, we investigated the phenotype and molecular defects of the offspring of poorly controlled diabetic female mice generated by streptozotocin (STZ) administration. Offspring was exposed to maternal diabetes during pregnancy and lactation. The body weight of STZ offspring was lower than that of control offspring at birth and in adulthood, and glucose tolerance was impaired in adult STZ offspring. Interestingly, the phenotype was more pronounced in male offspring. We next investigated the morphology of islets and expression of β cell-related genes, but no significant changes were observed. However, transcriptome analysis of the liver revealed activation of the fork head box protein O1 (Foxo1) pathway in STZ male offspring. Notably, two key gluconeogenesis enzyme genes, glucose 6 phosphatase catalytic subunit (G6pc) and phosphoenolpyruvate carboxykinase 1 (Pck1), were upregulated. Consistent with this finding, phosphorylation of Foxo1 was decreased in the liver of STZ male offspring. These changes were not obvious in female offspring. The activation of Foxo1 and gluconeogenesis in the liver may have contributed to the impaired glucose tolerance of STZ male offspring.

Introduction:The prevalence of waterpipe tobacco smoke (WTS) consumption is increased among pregnant woman. Prenatal cigarette smoke exposure increased the risk of developing cardiovascular diseases in offspring. The current study examined the effect of prenatal WTS exposure on inflammatory profile, oxidative stress, and cardiac biomarkers in adult offspring rats.Methods:Female rats received WTS (2 hours per day) or fresh air 1 day prior to mating and throughout the pregnancy period. The body and heart masses were measured in male offspring rats. The level of oxidative stress biomarkers, nitrate, inflammatory mediators (interleukin 6 [IL-6], tumor necrosis factor alpha [TNF-α]), and gene expression of protein kinase C epsilon, angiotensin 2 receptor one, and transforming growth factor beta1 were measured in cardiac tissue homogenates of 13-week-old male offspring rats.Results:Prenatal WTS exposure reduced body weight and increased heart to body weight ratio ( P < .05). Prenatal WTS exposure did not affect oxidative stress biomarkers (superoxide dismutase, glutathione peroxidase, and thiobarbituric acid reactive substances) but significantly increased catalase activity and nitrate level ( P < .05) in cardiac tissue of adult male offspring rats. In addition, prenatal exposure to WTS did not affect cardiac level of TNF-α and IL-6 as well as the gene expression of different cardiac modulators in adult male offspring rats ( P > .05).Conclusion:Prenatal WTS exposure has detrimental consequences on adult offspring rats by increasing the ratio of heart to body mass, increasing the catalase activity and nitrate level in cardiac tissue of adult male offspring rats.

Evidence is building for an association between the level of anxiety experienced by a mother during pregnancy and offspring cognition and structural and functional brain correlates. The current study uses fMRI to examine the association between prenatal exposure to maternal anxiety and brain activity associated with endogenous versus exogenous cognitive control in 20-year-old males. Endogenous cognitive control refers to the ability to generate control over decisions, strategies, conflicting information and so on, from within oneself without external signals, while exogenous control is triggered by external signals. In line with previous results of this long-term follow-up study we found that 20-year-olds of mothers reporting high levels of anxiety during weeks 12-22 of pregnancy exhibited a different pattern of decision making in a Gambling paradigm requiring endogenous cognitive control, compared to adults of mothers reporting low to average levels of anxiety. Moreover, the blood oxygenation level dependent (BOLD) response in a number of prefrontal cortical areas was modulated by the level of antenatal maternal anxiety. In particular, a number of right lateralized clusters including inferior frontal junction, that were modulated in the adults of mothers reporting low to average levels of anxiety during pregnancy by a task manipulation of cognitive control, were not modulated by this manipulation in the adults of mothers reporting high levels of anxiety during pregnancy. These differences in brain functional correlates provide a neurobiological underpinning for the hypothesis of an association between exposure to maternal anxiety in the prenatal life period and a deficit in endogenous cognitive control in early adulthood.

The programming of hepatic lipid dysfunction in response to early cholesterol exposure and the influencing effects of postnatal diet is evaluated in apoEIn two separate studies, female mice are assigned to a standard chow (S) or a cholesterol-enriched chow (C) diet during gestation and lactation. Male offspring from each dam are weaned on a postnatal S or a hypercaloric western (W) diet resulting in four experimental groups: S-S and C-S (Experiment 1) and S-W and C-W (Experiment 2). At weaning, litters from hypercholesterolemic mothers weighed less (p 0.05) and pups had higher blood lipids, glucose, and hepatic cholesterol compared with pups from S-fed mothers. Adult C-S offspring demonstrate an atherogenic lipid profile and increased (p 0.05) hepatic cholesterol and triglyceride content with altered lipid regulatory mRNA expression and protein content compared with S-S offspring. Alternatively, no difference (p 0.05) is observed between S-W and C-W in serum and hepatic lipid profiles; however, serum AST and ALT are higher (p 0.05) in C-W versus S-W offspring.The degree of hepatic lipid deposition observed in adult offspring exposed to excessive early cholesterol is influenced by the postnatal diet.

The Centers for Disease Control and prevention estimates that 9.3% of adults in the United States have type 2 diabetes mellitus (T2DM), costing the nation over $245B each year in medical expenditures and reduced productivity. More personalized approaches to prevention that distinguish between individuals with high environmental versus biological risk for T2DM could further reduce public health burden. The present study provides an in-depth examination of the relationship between maternal age and age of T2DM onset in a sample of adults participating in 11 waves of the Health and Retirement Study between 1992 and 2012, as a potential way of disentangling biological and socioeconomic predictors of T2DM. Data for each participant was obtained from the wave in which he or she first reported being diagnosed with type II diabetes or the last wave observed. The final analytic sample consisted of 16,239 study participants. The main predictor variable utilized in the present study was maternal age, defined as the age of the mother (in years) at the birth of the participant. Cox proportional hazards regression was used to examine the effects of maternal age, demographics and health characteristics on time until type 2 diabetes onset. Advanced maternal age was a significant predictor of age of diabetes onset, operationalized quadratically and as the interaction between maternal age at birth and a binary indicator of whether the mother was ≥30 years at birth.

Exposure to environmental stimuli in one generation can produce altered behavioral and neurobiological phenotypes in descendants. Recent work has shown that parental exposure to cannabinoids alters the rewarding properties of other abused drugs in the subsequent generation. However, whether preconception Δ9-tetrahydrocannabinol (THC) administration modifies the affective properties of nicotine in offspring is unknown. To address this question, male and female rats (F0) received THC (0 or 1.5 mg/kg) throughout the adolescent window and were bred on PND 65. In Experiment 1, adult F1-THC and F1-Veh progeny (males and females) underwent nicotine locomotor sensitization procedures during which nicotine (0 or 0.4 mg/kg) was administered every other day for five exposures, and locomotor activity was recorded on each exposure followed by a final nicotine challenge. There was no cross-generational effect of THC on nicotine locomotor sensitization, although acute exposure to nicotine produced greater activity in females relative to males independent of THC history. In Experiment 2, adult F1-THC and F1-Veh progeny (males and females) were implanted with jugular catheters and trained to self-administer nicotine (0.03 mg/kg/infusion). Following acquisition, all subjects were allowed to self-administer nicotine on a number of reinforcement schedules, e.g., FR2, FR5 and PR, followed by dose response and extinction procedures. Across all indices, F1-THC and F1-Veh subjects displayed similar IVSA of nicotine with no sex differences. The fact that there was no evidence of cross-generational effects of THC on nicotine suggests that such effects are drug-specific.

Publisher's version (útgefin grein), Emerging evidence suggests that parents’ preconception exposures may influence offspring health. We aimed to investigate maternal and paternal smoking onset in specific time windows in relation to offspring body mass index (BMI) and fat mass index (FMI). We investigated fathers (n = 2111) and mothers (n = 2569) aged 39–65 years, of the population based RHINE and ECRHS studies, and their offspring aged 18–49 years (n = 6487, mean age 29.6 years) who participated in the RHINESSA study. BMI was calculated from self-reported height and weight, and FMI was estimated from bioelectrical impedance measures in a subsample. Associations with parental smoking were analysed with generalized linear regression adjusting for parental education and clustering by study centre and family. Interactions between offspring sex were analysed, as was mediation by parental pack years, parental BMI, offspring smoking and offspring birthweight. Fathers’ smoking onset before conception of the offspring (onset ≥15 years) was associated with higher BMI in the offspring when adult (β 0.551, 95%CI: 0.174–0.929, p = 0.004). Mothers’ preconception and postnatal smoking onset was associated with higher offspring BMI (onset, Co-ordination of the RHINESSA study has received funding from the Research Council of Norway (Grants No. 274767, 214123, 228174, 230827 and 273838), ERC StG project BRuSH #804199, the European Union's Horizon 2020 research and innovation program under grant agreement No. 633212 (the ALEC Study WP2), the Bergen Medical Research Foundation, and the Western Norwegian Regional Health Authorities (Grants No. 912011, 911892 and 911631). Study centres have further received local funding from the following: Bergen: the above grants for study establishment and co-ordination, and, in addition, World University Network (RDF and Sustainability grant), Norwegian Labour Inspection, and the Norwegian Asthma and Allergy Association. Albacete and Huelva: SEPAR. Fondo de Investigación Sanitaria (FIS PS09). Gøteborg, Umeå and Uppsala: the Swedish Lung Foundation, the Swedish Asthma and Allergy Association. Reykjavik: Iceland University. Melbourne: NHMRC, Melbourne University, Tartu: the Estonian Research Council (Grant No. PUT562). Århus: The Danish Wood Foundation (Grant No. 444508795), the Danish Working Environment Authority (Grant No. 20150067134). The RHINE study received funding by Norwegian Research Council, Norwegian Asthma and Allergy Association, Danish Lung Association, Swedish Heart and Lung Foundation, Vårdal Foundation for Health Care Science and Allergy Research, Swedish Asthma and Allergy Association, Swedish Lung Foundation, Icelandic Research Council, and Estonian Science Foundation. The co-ordination of ECRHS was supported by European Union's Horizon 2020 research and innovation program under grant agreement No. 633212 (the ALEC Study), the European Commission frameworks 5 and 7 (ECRHS I and II) and the Medical Research Council (ECRHS III).

Background Schizophrenia has been associated with pregnancy and birth complications, and fetal exposure to inflammation is thought to be a common underlying mechanism. However, it is unclear whether the risk associated with inflammation is specific to particular phases of pregnancy, as no prior studies have examined maternal serum samples across multiple assessments from the first trimester onward. This study examined differences in longitudinal patterns of maternal serum levels of TNFa, IL-1b, IL-5, IL-6, IL-8, IL-10, and IL-17a across pregnancy for offspring who were later ascertained as having a psychotic disorder diagnosis, non-psychotic siblings of these cases, and unrelated, non-psychotic individuals who served as controls. Methods Participants included 90 offspring, 79 siblings, and 273 matched controls from the Philadelphia cohort of the National Collaborative Perinatal Project. Psychotic disorder diagnoses in adulthood were assessed with review of medical records and were confirmed with a validation study. Cytokine levels were assessed using a multiplex bead assay in archived maternal serum samples collected across prenatal visits and birth. Results Levels of pro-inflammatory TNFa, IL-1b, and IL-6 were significantly higher in maternal serum of offspring who later developed psychosis relative to maternal serum of non-psychotic siblings and matched controls. These differences were maximal in first half of pregnancy (7–20 weeks), tapering to non-significant during the second half of pregnancy. Discussion These findings elucidate the importance of exposure to elevated maternal pro-inflammatory cytokine levels in early pregnancy to the etiology of psychosis.

Mutations in the ligand-activated transcription factor PPARγ result in hypertension, and synthetic agonists of PPARγ reduce blood pressure. Previously we found that mice expressing dominant-negative (DN) PPARγ driven by an endothelium-specific promoter (E-DN) exhibit vascular dysfunction. Preeclampsia (PE) is a hypertensive disorder of pregnancy which carries cardiovascular risk to offspring. PE is also associated with vascular dysfunction. We hypothesized a role for endothelial PPARγ in the pathogenesis of PE and its sequelae. C57BL/6J dams were bred with E-DN sires, and symptoms of PE were induced by infusion of vasopressin (AVP, 24 ng/hr sc) throughout gestation. Phenotypes of PE were first assessed in pregnant dams and then in adult offspring. Compared to saline infusion (SAL), AVP elevated maternal blood pressure (SBP: 116±3 vs 107±3, p

The peak incidence of many psychiatric disorders occurs during emerging adulthood.1 The ongoing, community-based National Longitudinal Lesbian Family Study (NLLFS), which has a 92% retention rate, has followed a cohort of offspring with sexual-minority parents.2 This longitudinal study (from conception into adulthood) provides the opportunity to examine mental health status in these adult offspring.

Co-use of cannabis and tobacco is increasingly common among women and is associated with tobacco and cannabis dependence and poorer cessation outcomes. However, no study has examined maternal patterns of co-use over time, or the impact of maternal co-use on co-use and drug problems in adult offspring. Pregnant women (M age = 23, range = 18–42; 52% African American, 48% White) were asked about substance use during each trimester of pregnancy, and at 8 and 18 months, 3, 6, 10, 14, 16, and 22 years postpartum. We examined patterns of any maternal cigarette and cannabis use during pregnancy and the postpartum years. As young adults (M age = 22.8 years, range = 21–26), 603 offspring completed the Diagnostic Interview Schedule (DIS). Growth mixture modeling (GMM) was used to identify four maternal trajectories through 16 years postpartum: (1) no co-use (66%), (2) decreasing co-use (16%), (3) postpartum-only co-use (11%), and (4) chronic co-use (7%). Offspring whose mothers were in the decreasing co-use group (co-users primarily during prenatal and preschool periods) were more likely to be co-users than the offspring of non-co-users. Offspring whose mothers were chronic co-users of cigarettes and cannabis were more than twice as likely to have a drug use disorder than young adults whose mothers were not co-users. The results of this study highlight the heterogeneity in maternal co-use of tobacco and cannabis over time, with some women quitting during pregnancy but resuming co-use in the postpartum, and other women co-using during pregnancy but desisting co-use over time. Maternal trajectories of co-use were associated with inter-generational transfer of risk for substance use and dependence in adult offspring.

BACKGROUND: Birth by Cesarean section (C-section) may increase the risk for non-communicable diseases. We aimed to examine the relation of birth by C-section with offspring overweight and markers of cardiometabolic risk in a prospective observational cohort with 20 years of follow-up.METHODS: The Danish Fetal Origins Cohort enrolled 965 pregnant women in 1988-1989. In 2008, a follow-up study of the offspring was completed. The offspring were invited to participate in a clinical examination with measurements of anthropometry and a fasting blood sample (n=443). In addition, 252 offspring completed a self-administered questionnaire with questions on height and weight, leaving us with a study sample of 695 offspring. Offspring overweight at 20 years was defined as body mass index (BMI)⩾25 kg m-2. We also analyzed blood pressure and fasting blood samples for cardiometabolic risk factors including insulin, leptin and adiponectin, and lipid concentrations.RESULTS: In the cohort, 7% were born by C-section, and at age 20 years, 18% of the offspring had a BMI ⩾25 kg m-2. Birth by C-section was associated with increased odds of overweight or obesity at 20 years (Odds ratio=2.17 (95% confidence interval (CI): 1.10, 4.27)) after adjustment for potential confounders. Birth by C-section was also associated with higher serum concentrations of total cholesterol (8.5%, 95% CI: 1.1-16.5), low-density lipoprotein cholesterol (12.6%, 95% CI: 1.0, 25.5), leptin (73.1%, 95% CI: 5.9, 183.1) and Apolipoprotein B (0.08 g l-1, 95% CI: 0.04, 0.15). In contrast, birth by C-section was not related to blood pressure or serum concentrations of insulin, adiponectin, triglycerides, high-density lipoprotein or Apolipoprotein A.CONCLUSION: Birth by C-section was associated with higher frequency of dysmetabolic traits in offspring independently of shared risk factors. Further research aimed at replicating these findings and elucidating the underlying biological mechanisms of this relation is needed.International Journal of Obesity advance online publication, 22 August 2017; doi:10.1038/ijo.2017.175.

An important avenue for smoking deterrence may be through familial ties if adult smokers respond to parental healthshocks. In this paper, we merge the Original Cohort and the Offspring Cohort of the Framingham Heart Study to study howadult offspring smoking behavior and subjective health assessments vary with elder parent smoking behavior and healthoutcomes. These data allow us to model the smoking behavior of adult offspring over a 30-year period contemporaneouslywith parental behaviors and outcomes. We find strong ‘like father, like son’ and ‘like mother, like daughter’ correlationsin smoking behavior. We find that adult offspring significantly curtail their own smoking following an own health shock;however, we find limited evidence that offspring smoking behavior is sensitive to parent health, with the notable exceptionthat women significantly reduce both their smoking participation and intensity following a smoking-related cardiovascularevent of a parent. We also model the subjective health assessment of adult offspring as a function of parent health, and wefind that women report significantly worse health following the smoking-related death of a parent. Copyright © 2015 JohnWiley & Sons, Ltd.Received 7 November 2013; Revised 12 February 2015; Accepted 9 April 2015

Our previous study demonstrated that Staphylococcal enterotoxin B (SEB) administration during pregnancy could alter the percentage of T cells subpopulation in the thymus of the neonatal rats; however, little is known about the effect of maternal SEB administration during pregnancy on T cells subpopulation in the peripheral blood of the offspring rats. In the present study, pregnant rats at gestational day 16 were intravenously injected with 15 µg SEB. The present study found that prenatal exposure to SEB significantly decreased the percentages of CD8 T cells in the peripheral blood of both neonatal rats on the fifth day after delivery and the adult offspring rats. Furthermore, it significantly increased the percentage of CD4 T cells as well as the ratios of CD4 to CD8 T cells in both neonatal and adult offspring rats. Prenatal exposure to SEB significantly decreased the expression levels of IL-4 and IFN-γ in the plasma of neonatal and adult offspring rats. Furthermore, SEB restimulation significantly increased the percentage of CD8 T cells and significantly decreased the percentage of CD4 T cells. These data suggest the prenatal exposure to SEB can imprint the increased CD4:CD8 T cell ratio in the peripheral blood from the neonate to adulthood through the decreased CD8 T cells and the increased CD4 T cells, and altered the response characteristics of CD4 and CD8 T cells to secondary SEB administration in the peripheral blood of the adult offspring rats.

It is unclear whether any breastfeeding or a certain duration of breastfeeding is protective against the development of diabetes in adult offspring.We followed a sub-sample of 3,595 offspring born in the Mater Hospital in Brisbane, Australia between 1981 and 1983 and for whom we had doctor diagnosed self-reported diabetes at age 21 years and maternal reported duration of breastfeeding at 6-month post-natal follow-up. Multiple logistic regression was used to examine the independent associations of duration of breastfeeding (never breastfeed, breastfed4 months and breastfed ≥4 months) with offspring diabetes by age 21 years.Of 3,595 young adults, 45 (1.25 %) developed diabetes by age 21 years. The odds ratio of experiencing diabetes was 0.58 (95 % CI 0.29, 1.16) for offspring who were breastfed4 months, and it was 0.29 (95 % CI 0.13, 0.63), for offspring who were breastfed at least 4 months compared to the never breastfed offspring. Adjusting for potential confounding and mediating factors including maternal age, education, pre-pregnancy body mass index (BMI), smoking, offspring sports, TV and their BMI at 21 years did not substantially alter this association.Findings of this study suggest that infants who are breastfed for longer than 4 months have a substantial protective effect against the development of diabetes in young adulthood, which is independent of current BMI. Promoting breastfeeding for a minimum of 4 months may be a useful strategy for the prevention of diabetes among young adults.