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Annual reproductive success and senescence patterns vary substantially among individuals in the wild. However, it is still seldom considered that senescence may not only affect an individual but also affect age-specific reproductive success in its offspring, generating transgenerational reproductive senescence. We used long-term data from wild yellow-bellied marmots ( Marmota flaviventer ) living in two different elevational environments to quantify age-specific reproductive success of daughters born to mothers differing in age. Contrary to prediction, daughters born to older mothers had greater annual reproductive success on average than daughters born to younger mothers, and this translated into greater lifetime reproductive success. However, in the favorable lower elevation environment, daughters born to older mothers also had greater age-specific decreases in annual reproductive success. In the harsher higher elevation environment on the other hand, daughters born to older mothers tended to die before reaching ages at which such senescent decreases could be observed. Our study highlights the importance of incorporating environment-specific transgenerational parent age effects on adult offspring age-specific life-history traits to fully understand the substantial variation observed in senescence patterns in wild populations.

CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior Estudos experimentais e em humanos demonstram que alterações no ambiente intrauterino podem programar doenças na vida adulta da progênie. Sendo assim, este trabalho teve como objetivo avaliar as possíveis alterações renais na prole adulta de ratas Wistar expostas à dieta hiperlipídica, com diferentes teores de lipídeos, durante a gestação e lactação. Para isso, foram utilizados ratos Wistar machos e fêmeas para acasalamento. Uma vez grávidas, as ratas e seus filhotes fêmeas de 120 dias foram divididos nos grupos: 1) Controle - C: filhotes (n=10) de mães que receberam dieta comercial (3,5% de lipídeos); 2) Experimental 1 – E1: filhotes (n=10) de mães que receberam dieta hiperlipídica com 28% de lipídeos; 3) Experimental 2: filhotes (n=10) de mães que receberam dieta hiperlipídica com 40% de lipídeos. Foram avaliados parâmetros maternos como consumos hídrico, alimentar, calórico diário e de macronutrientes e variação de peso corporal na gestação; e parâmetros da prole como determinação da taxa de filtração glomerular (TFG), excreção urinária de proteínas (EUP), níveis plasmáticos de triglicerídeos (TG), colesterol total (CT) e glicemia e coleta dos rins para quantificação de colágeno cortical e estudos morfométricos e imunohistoquímicos. Já as ratas de E1 ingeriram mais calorias que os demais grupos e, juntamente com as mães de E2, consumiram mais lipídeos. A porcentagem de colágeno total e de colágeno tipo I foi maior nos grupos experimentais, principalmente em E1, e a porcentagem de colágeno tipo III foi maior em E2. Os animais de E2 apresentaram maior número de células em proliferação no compartimento tubulointersticial (TBI) renal e juntamente com os de E1 tiveram maior expressão de alfa-actina glomerular, que foi mais evidente em E1, assim como a expressão TBI. Os 2 grupos experimentais, principalmente E1, também apresentaram maior expressão glomerular de desmina. Não houve diferenças significativas entre os grupos nos estudos morfométricos, nem nos níveis plasmáticos de CT e TG e glicemia, mas os animais de E1 apresentaram redução da TFG. O consumo materno de dietas hiperlipídicas, durante a gestação e lactação, pode programar alterações renais importantes na prole adulta de ratas Wistar, mas de magnitude e tipo diferentes, dependendo do teor de lipídeos da dieta. Experimental and human studies demonstrate that changes in the intrauterine environment can program diseases in the adult life of the progeny. Thus, this study aimed to evaluate possible renal changes in the adult offspring from Wistar rats exposed to a high-fat diet, with different levels of lipids, during pregnancy and lactation. For this, male and female Wistar rats were used for mating. Once pregnant, the rats and their 120-day old female pups were divided into groups: 1) Control - C: pups (n = 10) from dams who received a commercial diet (3.5% lipids); 2) Experimental 1 - E1: pups (n = 10) from dams who received a high-fat diet with 28% lipids; 3) Experimental 2: pups (n = 10) from dams who received a high fat diet with 40% lipids. Maternal parameters were evaluated, such as water, food, daily caloric and macronutrient consumption and body weight variation during pregnancy; and offspring parameters such as determination of glomerular filtration rate (GFR), urinary protein excretion (EUP), plasma triglyceride levels (TG), total cholesterol (TC) and blood glucose and kidney collection for quantification of cortical collagen and morphometric and immunohistochemistry studies. E2 dams consumed less food than E1 , in addition to less carbohydrates and proteins. The E1 dams consumed more calories than the other groups and, together with the E2 dams, consumed more lipids. The percentage of total collagen and type I collagen was higher in the experimental groups, mainly in E1, and the percentage of type III collagen was higher in E2. The animals from E2 showed a greater number of proliferating cells in the renal tubulointerstitial compartment (TBI) and, together with those of E1, they had greater expression of glomerular alpha-actin, which was more evident in E1, as well as the expression of TBI. The experimental groups, mainly E1, also showed greater glomerular expression of desmin. There were no significant differences between the groups in the morphometric studies, nor in the plasma levels of CT and TG and glycemia, but the E1 animals showed a reduction in GFR. Maternal consumption of high-fat diets, during pregnancy and lactation, can schedule important renal changes in the adult offspring of Wistar rats, but of different magnitude and type, depending on the lipid content of the diet. Dissertação (Mestrado) 2023-05-04

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.

Intrauterine or early postnatal high-fat diet (HFD) has substantial influences on adult offspring health; however, studies of HFD-induced maternal obesity on regulation of adult offspring bone formation are sparse. Here, we investigated the effects of HFD-induced maternal obesity on both fetal and adult offspring skeletal development. We found that HFD-induced maternal obesity significantly decreased fetal skeletal development, but enhanced fetal osteoblastic cell senescence signaling and significantly increased the expression of inflammatory factors of the senescence-associated secretory phenotype (SASP) in osteo-progenitors. It was found that p300/CBP activation led to H3K27 acetylation to increase the expression of senescence-related genes and PPARγ in embryonic mouse osteogenic calvarial cells from HFD obese dams. These results were recapitulated in human umbilical cord mesenchymal stem cells (UC MSCs) isolated from offspring of pregnant obese and lean mothers following delivery. Regardless of postnatal HFD challenge, adult offspring from HFD obese dams showed significantly suppressed bone formation. Such early involution of bone formation of adult offspring from HFD obese dams may at least in part due to histone acetylation, i.e., epigenetic regulation of genes involved in cell senescence signaling in pre-osteoblasts from prenatal development. These findings indicate fetal pre-osteoblastic cell senescence signaling is epigenetically regulated by maternal obesity to repress bone formation in adult offspring in rodents and suggest that at least some of these effects may also manifest in humans.

Fetal metabolic programming caused by the adverse intrauterine environment can induce metabolic syndrome in adult offspring. Adverse intrauterine environment introduces fetal long-term relatively irreversible changes in organs and metabolism, and thus causes fetal metabolic programming leading metabolic syndrome in adult offspring. Fetal metabolic programming of obesity and insulin resistance plays a key role in this process. The mechanism of fetal metabolic programming is still not very clear. It is suggested that epigenetic programming, also induced by the adverse intrauterine environment, is a critical underlying mechanism of fetal metabolic programming. Fetal epigenetic programming affects gene expression changes and cellular function through epigenetic modifications without DNA nucleotide sequence changes. Epigenetic modifications can be relatively stably retained and transmitted through mitosis and generations, and thereby induce the development of metabolic syndrome in adult offspring. This manuscript provides an overview of the critical role of epigenetic programming in fetal metabolic programming.

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.

Because of political conflicts and climate change, migration will be increased worldwide and integration in host societies is a challenge also for migrants. We hypothesize that migrants, who take up the challenge in a new social environment are taller than migrants who do not pose this challenge. We analyze by a questionnaire possible social, nutritional and ethnic influencing factors to body height (BH) of adult offspring of Turkish migrants (n = 82, 39 males) aged from 18 to 34 years (mean age 24.6 years). The results of multiple regression (downward selection) show that the more a male adult offspring of Turkish migrants feels like belonging to the Turkish culture, the smaller he is (95% CI, -3.79, -0.323). Further, the more a male adult offspring of Turkish migrants feels like belonging to the German culture, the taller he is (95% CI, -0.152, 1.738). We discussed it comparable to primates taking up their challenge in dominance, where as a result their body size increase is associated with higher IGF-1 level. IGF-1 is associated with emotional belonging and has a fundamental role in the regulation of metabolism and growth of the human body. With all pilot characteristics of our study results show that the successful challenge of integration in a new society is strongly associated with the emotional integration and identification in the sense of a personal sense of belonging to society. We discuss taller BH as a signal of social growth adjustment. In this sense, a secular trend of BH adaptation of migrants to hosts is a sign of integration.

The number of older parents ageing in tandem with their adult children with intellectual disability (ID) is increasing. This unique situation calls for greater research that investigates how older parents experience this extended care-giving role, including the extent to which they are engaging in futures planning. Participants were recruited via disability service providers in South Australia. Using the theoretical perspective of hermeneutic phenomenology to understand lived experiences, semi-structured in-depth interviews were carried out with older parents (N = 17, mean age 70 years). Six offspring were living in the family home while the remainder were in supported accommodation. Main themes to emerge from the data were: (a) perpetual parenting, (b) costs and rewards and (c) planning to plan. Parents were providing care across a range of areas, regardless of whether their offspring lived at home or in supported accommodation. While aware of the need to plan for the future, most did not have a firm plan in place. Parents are providing a high level of support to their adult children with ID regardless of whether they live in supported accommodation or the family home. While some have started to think about future care arrangements, most appear unclear over what the future holds.

Much is known about adult children caring for their aging parents, yet the potentially unique experience of offspring caring for traumatized parents is underexplored. Therefore, the current studies assessed filial anxiety and sense of obligation among offspring of Holocaust survivors (OHS) in caring for their parents.In Study 1, we interviewed 10 OHS (mean age = 61.0) in order to extract themes of filial anxiety. Based on Study 1's data, a newly constructed scale of filial anxiety was administered in Study 2 to 59 adult offspring (mean age = 56.4): 28 OHS and 31 comparisons. Study 3 included 143 dyads of parents and offspring (mean age = 55.4 and 81.7, respectively): 86 Holocaust dyads and 57 comparison dyads. Parents reported posttraumatic stress disorder (PTSD) symptoms and offspring reported filial anxiety and sense of obligation.In Study 1, interviewees referred to concerns about parent experiencing decline alongside caregiving difficulties. In Study 2, OHS reported higher filial anxiety and sense of obligation relative to comparisons. This group difference was mediated by sense of obligation. In Study 3, OHS with parental PTSD reported higher filial anxiety and sense of obligation relative to comparisons. Once more, filial sense of obligation served as a mediator. In Studies 2-3, results remained significant after adjusting for offspring symptoms.Parental exposure to the Holocaust, and especially parental PTSD, related to higher filial obligation, which in turn was related to higher filial anxiety. These findings bear important implications for practitioners working with survivors' families.

Social participation is an important resource for parents in old age, and may be particularly important for parents living with adult offspring with intellectual and developmental disabilities. To evaluate whether socializing with friends and family and participating in social organizations protects against depression in old age, this study examined parents of adult offspring with disabilities (n = 164) and without disabilities (n = 820). As expected, more socializing with friends and more participating in organizations were associated with fewer depressive symptoms for all parents. However, socializing with family members predicted fewer depressive symptoms only for parents co-residing with their adult offspring with disabilities, suggesting that socializing with family is particularly important for parents providing direct care to adults with disabilities.

This review examines what is known about estrangement between parents and their adult children in terms of definition, prevalence, causes, and consequences. Estrangement has been defined and conceptualised in different ways, although most definitions have focused on the negative quality of the relationship and the voluntarily or intentional decision of at least one family member to initiate and maintain distance. A diverse range of factors which are often interlinked has been found to contribute to estrangement. The consequences of estrangement from a parent or child include experiencing reduced levels of psychological well-being, feelings of loss, and experiences and/or perceptions of stigma. The estrangement literature has the potential to reveal variation in the quality of parent-child relationships in adulthood so that family scholars can move beyond our assumptions and understand family relationships as they are, rather than how they could or ‘should’ be.

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.

The lifetime risk for posttraumatic stress disorder (PTSD) and PTSD symptoms (PTSS) among primary and secondary female victims is known to be higher than for male. This study assessed gender differences in PTSS among former prisoners of war's (ex-POWs) adult offspring and the associations with their fathers' and mothers' PTSS and the parental bonding with them.A correlative study.A sample of 79 Israeli father-mother-offspring ex-POW triads from the 1973 Yom Kippur War completed self-report measures. Fathers were assessed in 2008, mothers were assessed in 2011 and their adult offspring took part in 2014.Sons of ex-POWs reported higher levels of PTSS as compared to daughters of ex-POWs. However, fathers' PTSS was positively related to daughters' PTSS, but not significantly related to sons' PTSS. Daughters' PTSS were also associated with both parents' lower care and higher overprotection, while sons' PTSS were associated only with fathers' lower care and higher overprotection.Among adult offspring of ex-POWs, sons are at greater risk for psychological distress in the form of PTSS. Nevertheless, the intergenerational transmission of captivity-related PTSS from both fathers and spouses to their offspring is more prominent among daughters of ex-POWs.

Background: The prevalence of divorce in Western countries has increased in recent decades. However, there is no recent systematic review and/or meta-analysis of studies testing for long-term effects of parental divorce on offspring affective disorders. The present study conducted a systematic review and meta-analysis of studies published since 1980 testing for the association between parental divorce and offspring depression and anxiety in adulthood.\ud \ud Method: PUBMED, Science Direct, Medline, PsychInfo, and PsychArticles databases were searched for eligible studies. Random-effect meta-analyses were used to synthesize effect sizes and to test whether associations of parental divorce with offspring affective disorders differed among three publication periods (i.e., before 1996, 1996–2005, 2006–2015).\ud \ud Results: In total, 29 studies were eligible for the systematic review, and 18 studies were included in the meta-analyses (depression: n=21,581; anxiety: n=2472). There was significant association between parental divorce and offspring depression (OR=1.56; 95%CI [1.31, 1.86]), but not anxiety (OR=1.16; 95%CI [0.98, 1.38]). The effect of parental divorce on offspring depression was not weaker in the reports published in more recent decades.\ud \ud Limitations: There is limited research in relation to offspring anxiety in adulthood.\ud \ud Conclusions: Parental divorce is associated with an increased risk of adult offspring depression, with no indication of the effect being weaker in recent publications.

Background: The increased longevity of individuals with intellectual disability means that ageing parents often play an extended caregiving role into late life. This systematic review evaluates qualitative evidence on futures planning among older parents whose adult children live either in the family home or out-of-home. Method: Electronic databases were searched for studies published between 2000 and 2015. Studies that met the inclusion criteria were analysed using the McMaster Critical Review Form for Qualitative Studies. Results: Of 14 articles reviewed, quality was mixed. Three over-arching themes emerged: (1) external barriers to planning involving reservations about available services; (2) internal barriers preventing parents from planning such as mutual dependency and sense of helplessness; and (3) existence of diverse “plans” and ways of managing the future. Conclusions: Parents are aware of the need to make plans or at the very least have preferences for what they would like to occur. However, a range of external and internal factors pose as barriers to this process. Refereed/Peer-reviewed

This study aimed to assess the longitudinal associations between the 1973 Israeli-Arab War ex-prisoners of war’s (ex-POWs) posttraumatic stress disorder symptoms (PTSS) and dyadic adjustment (DAS) and their adult offspring’s secondary PTSS and DAS. A sample of 124 Israeli father–child dyads has been examined (fathers at 2003 and 2008; offspring at 2013–2014). Results show that fathers’ PTSS and DAS mediated the link between war captivity and offspring’s secondary PTSS and DAS, respectively. The intergenerational transmission of captivity trauma is indirectly explained by the long-term effects of the fathers’ PTSS on their offspring’s secondary PTSS and DAS.

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.

Metabolites regulated by the microbiota of pregnant mice modulates the developing embryonic brain and influences thalamocortical axon formation and subsequent sensorimotor behaviour in adult offspring.

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.

Author(s): Goldberg, Rachel E; Tienda, Marta; Eilers, Michelle; McLanahan, Sara S | Abstract: Objective:This study examines intergenerational continuities in relationship instability, general relationship quality, and intimate partner violence (IPV) between mothers and adolescents. Background:A growing body of literature has observed similarities in relationship quality between parents and their adult offspring. Less attention has focused on whether intergenerational continuities are present in adolescent relationships. Method:Using age 3, 5, 9, and 15 data from the Fragile Families and Child Wellbeing birth cohort study (N=3,162), the authors examined associations between maternal reports of relationship instability, general quality, and IPV in early and middle childhood and similar adolescent reports at age 15. Variations based on timing and persistence of exposures were considered. Results:In general, exposures to low-quality maternal relationships were associated with higher risk of forming adolescent partnerships and lower relationship quality. Intergenerational links in quality were predominantly construct-specific, consistent with observational learning processes. Adolescents exposed to maternal relationships of poor general quality in middle childhood were less likely to report high-quality relationships themselves, and those exposed to any maternal physical IPV victimization during childhood were more likely to perpetrate IPV in their own relationships. Exposure to maternal relationship instability in both early and middle childhood was associated with more adolescent romantic partners. Conclusion:The study illuminates additional pathways through which healthy and unhealthy relationships are reproduced across generations.

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.

Resveratrol (RSV) can protect against non-communicable diseases by improving cholesterol metabolism. However, it is unclear that effects of maternal RSV intake on health of adult offspring. In this study, we examined effects of maternal RSV intake during lactation on cholesterol metabolism in adult male rat offspring. Female Wistar rats were fed a control diet (CON) supplemented with or without RSV (20 mg/kg body weight/day) during their lactation period. Male offspring were weaned onto a standard diet and maintained on this diet for 36 weeks. As a result, plasma cholesterol level significantly decreased in RSV offspring compared to CON offspring. Furthermore, a decrease in hepatic 3-hydroxy-3-methylglutaryl-CoA reductase level and an increase in hepatic LDL-receptor level were observed in the RSV offspring. These results indicate that maternal RSV intake causes long-term decrease in plasma cholesterol level in the offspring through suppression of hepatic cholesterol biosynthesis and promotion of hepatic cholesterol uptake.

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.

The experiences of mothers of adult offspring with a dual diagnosis have rarely been discussed in the literature, despite growing involvement and responsibility of mothers for daily care of their children. Interpretive phenomenological analysis of in-depth interviews was used to examine the mothering experience of 12 mothers of adult offspring with dual diagnosis. The analysis revealed that the mothers' experiences were intensive, abusive, and isolating, and simultaneously rendered them invisible, undervalued, or ignored by professionals, community, and family. Furthermore, the analysis indicated that this experience of 'intensive-invisible' mothering was promoted or prevented by three intersecting mechanisms, identified here as discursive, institutional, and spatial. The research contributes to the fields of knowledge regarding family members of people with mental health problems, by adding a theoretical layer that takes into account how public discourses of motherhood mould women's accounts of their mothering experience. Practical implications of these findings for professionals working with these mothers are discussed. Specifically, therapeutic intervention that focuses on identifying and modifying the underlying psychological and social processes associated with the 'intensive-invisible' mothering experience could be useful.

Emerging evidence suggests environmental contaminant exposures during critical windows of development may contribute to the increasing prevalence of obesity. It has been shown that early life polybrominated diphenyl ethers exposures have critical impacts on child weight trajectories, however, little is known about their maternal mechanisms responsible for offspring obesity development. In this study, we investigated the effects of perigestational low-dose 2, 2′, 4, 4′-tetrabromodiphenyl ether (BDE-47) exposure on maternal metabolome, and its possible link to adult offspring bodyweight changes. Female Sprague-Dawley rats were exposed to daily doses of 0.1, or 1 mg/kg BDE-47 from 10 days prior to conception until offspring were weaned on postnatal day 21, and then a gas chromatography-mass spectrometry based metabolomics analysis was used to uncover the global metabolic response in dams. The pups continued to grow into adulthood for measurements of bodyweight. Perigestational BDE-47 exposure caused increased adult bodyweight in male but not in female offspring and dams. Metabolomics revealed significant changes in maternal serum metabolites that clearly distinguish BDE-47 from control rats. These differentially expressed metabolites were primarily implicated in amino acid, lipid, carbohydrate, and energy metabolisms, which was confirmed by pathway analysis. Importantly, most of these identified metabolites were decreased, a state similar to maternal malnutrition that can predispose adult male offspring to weight increase and adiposity in a postnatal environment with abundant calories. Collectively, our data suggest that perigestational exposure to low-dose BDE-47 produces altered maternal serum metabolome, which may be an additional contributing factor to weight gain in adult male offspring.

BACKGROUND: Rodent models of maternal immune activation (MIA) are used as an experimental approach for neurodevelopmental disorders such as schizophrenia to study neuronal and behavioral dysfunctions of offspring. In particular, injection of the viral mimic poly(I:C) in pregnant mice causes disruption of neuronal development of the offspring leading to deficits in social behavior, cognition, sensorimotor processing and/or dopaminergic system in adulthood [1]. BI 409306 is a selective phosphodiesterase-9 (PDE9) inhibitor [2] currently under development for the prevention of relapse in patients with schizophrenia taking antipsychotic medications (NCT03351244). PDE9 inhibition is hypothesized to improve the NMDA-receptor signaling cascade by increasing cGMP levels which subsequently leads to strengthening of synaptic plasticity. Abnormalities in glutamatergic neurotransmission related to NMDA-receptor hypofunction, along with dysfunction of the dopaminergic circuitry, are believed to play a crucial role in the pathophysiology of schizophrenia. In this study, we have investigated the effect of BI 409306 on the behavioral deficits of adult offspring from the poly(I:C)-based MIA mouse model. METHODS: Pregnant C57BL6/N mice were treated with poly(I:C) (5 mg/kg, i.v.) or control (saline, i.v.) solution on gestation day 12. All male offspring (n=9/group) were administered orally once daily with BI 409306 (0.2, 0.5 or 1 mg/kg) or vehicle starting at post-natal day (PND) 70 until subjected to a battery of consecutive behavioral tests two weeks later which lasts until PND120. The order of these tests were: Y-maze spontaneous alternation for working memory performance, social interaction to assess social behavior, pre-pulse inhibition (PPI) for sensorimotor processing and amphetamine-induced hyperlocomotion to assess the dopaminergic system. Statistical analyses were done by one-way ANOVA followed by Fisher’s LSD post-hoc. RESULTS: Maternal poly(I:C)-induced immune challenge led to a significant decrease in social interaction (p

Background: Maternal nutrition is a pivotal factor in determining long-term energy homeostasis in the offspring. However, whether resveratrol (R), with antioxidant and anti-obesity actions, can improve the long-term impact of poor maternal nutrition on the physiological function of white adipose tissue in the offspring is unknown. We previously reported that maternal resveratrol intake during pregnancy and lactation has long-term effects on metabolism in the offspring and these effects depend on the type of diet ingested by the mother and on the offspring’s sex. Aim: Our aim was to further analyze whether resveratrol supplementation during pregnancy and lactation induces changes in visceral adipose tissue morphology in the adult offspring. Materials and Methods: Female Wistar rats received a low-fat diet (LFD; 3.8 Kcal/g, 10.2% fat) or a high fat diet (HFD; 5.1 Kcal/g, 61.6% fat) during pregnancy and lactation. Half of each group received resveratrol (R) in their drinking water (50 mg/L; intake 2.0-2.5 mg/Kg/day). Offspring were weighed at birth and then weaned onto standard chow on postnatal day (PND) 21. Body weight (BW) and energy intake (EI) were measured weekly until PND150 when they were sacrificed. The visceral adipose tissue (VAT) depot was weighed and histomorphometric analysis of hematoxylin and eosin-stained histological sections was conducted using image-processing software (Adiposoft-ImageJ). Data are expressed as mean ± SD (parametric analyses) or interquartile range (non-parametric analyses). Results: On PND150, male offspring from HFD dams weighed more and had more VAT than those from LFD dams (p

Two studies assessed the nature of parental communication about the trauma of Indian Residential Schools (IRSs) in relation to the psychological distress of their adult offspring, and whether the link between parental communication and distress was mediated by offsprings’ greater awareness of collective discrimination or sense of pride in cultural identity. In Study 1, an online survey of Indigenous participants from across Canada ( N = 498) demonstrated a curvilinear relation between the extent to which parents talked about their negative IRS experiences and the severity of depressive symptoms among offspring, among whom symptoms were particularly pronounced with more frequent communication. This relation was mediated by greater perceived discrimination. A similar, but inverse, association was found when parental communications conveyed positive construals of their IRS experiences. Study 2 ( N = 134) further demonstrated an association between direct communications from IRS survivors and offspring wellbeing in that, either the absence of, or especially frequent communications were related to more severe depressive symptoms among offspring. However, hearing about parental IRS experiences from someone other than the parent was not related to offsprings’ depressive symptoms. Qualitative analyses indicated that direct communications from parents tended to provide excessive detail, whereas parental silence was associated with speculation and feelings of isolation or resentment among offspring of IRS survivors. Taken together, the results suggest that either insufficient or excessive parental communication about trauma might undermine offspring wellbeing, whereas moderate levels of communication that provide positive meaning and promote cultural pride or diminish perceptions of personal discrimination could be beneficial.