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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.

The association between maternal metabolic status at the time of conception and subsequent embryogenesis and offspring development has been studied in detail. However, less attention has been given to the significance of paternal nutrition and metabolism in directing offspring health. Despite this disparity, emerging evidence has begun to highlight an important connection between paternal metabolic well-being, semen quality, embryonic development and ultimately adult offspring health. This has established a new component within the Developmental Origins of Health and Disease hypothesis. Building on the decades of understanding and insight derived from the numerous models of maternal programming, attention is now becoming focused on defining the mechanisms underlying the links between paternal well-being, post-fertilisation development and offspring health. Understanding how the health and fitness of the father impact on semen quality is of fundamental importance for providing better information to intending fathers. Furthermore, assisted reproductive practices such as in vitro fertilisation rely on our ability to select the best quality sperm from a diverse and heterogeneous population. With considerable advances in sequencing capabilities, our understanding of the molecular and epigenetic composition of the sperm and seminal plasma, and their association with male metabolic health, has developed dramatically over recent years. This review will summarise our current understanding of how a father's metabolic status at the time of conception can affect sperm quality, post-fertilisation embryonic and fetal development and offspring health.

The current paper aims to summarize the psychological literature on offspring who are over the age of 18 at the time of their parents’ divorce. The current review identifies the impact of divorce o...

ObjectiveTo study how adult offspring in planned lesbian-parent families relate to their unknown or known donors.DesignQualitative analyses of the sixth wave of online surveys from a longitudinal study of adult offspring in planned lesbian families, enrolled at conception.SettingCommunity-based United States national study.Patient(s)The 76 participants were 25-year-old donor insemination (DI) offspring whose lesbian parent(s) enrolled in a prospective longitudinal study when these offspring were conceived.Intervention(s)None.Main Outcome Measure(s)Offspring were asked about donor type, feelings about permanently unknown donor, satisfaction with and role of known donor, whether relationship with known donor was ongoing, and age of meeting open-identity donor.Result(s)This cohort (n = 76) of DI offspring with lesbian parents was among the first generation to reach adulthood. Thirty participants had permanently unknown donors and most participants felt comfortable about not knowing them. Sixteen participants had open-identity donors they had not met. Thirty had currently known donors—met in childhood (n = 22) or after open-identity donor disclosure (n = 8)—of whom two thirds had ongoing relationships with donors, half considered their donors as acquaintances, and nearly half had good feelings about their relationship, although a minority expressed conflicted feelings.Conclusion(s)This study of adult DI offspring from planned lesbian families shows that those who knew their donors mainly felt positively about these relationships. Qualitative analyses offered insight into offspring-donor relationships, whose numbers are increasing due to historical and demographic trends.

Background: Maternal lipid intake in the early postnatal period has a long-term effect on the possibility of fatty liver formation in children; besides, the importance of lipid consumption during lactation for children's health has been suggested. Green tea extract (GTE) contains abundant catechins, and it has been reported to improve lipid metabolism and prevent fatty liver. Objective: The aim of this study was to examine the effects of maternal GTE intake during lactation on hepatic lipid accumulation in adult male rats exposed to a continuous high-fat (HF) diet from the foetal period. Methods: Pregnant Wistar rats received diets containing 13% (control-fat, CON) or 45% (high-fat, HF) fat. CON-fed mothers received the same diet during lactation, whereas HF-fed mothers received either HF diet alone or HF diet supplemented with 0.24% GTE. At weaning, male offspring were divided into three groups, i.e. CON/CON/CON, HF/HF/HF (HF-offspring) or HF/HF+GTE/HF (GTE-offspring), and were fed until 51 weeks. Results: A significant hepatic triglyceride (Tg) accumulation was observed in the HF-offspring when compared with the other offspring. This is presumed to be caused by the promotion of Tg synthesis derived from exogenous fatty acid due to a significant increase in diacylglycerol O-acyltransferase 1 and a decrease in Tg -expenditure caused by decreasing microsomal triglyceride transfer protein (MTTP) and long-chain acyl-CoA dehydrogenase. On the other hand, attenuated hepatic Tg accumulation was observed in the GTE-offspring. The levels of the hepatic lipid metabolism-related enzymes were improved to the same level as the CON-offspring, and particularly, MTTP was significantly increased as compared with the HF-offspring. Conclusion: This study indicates the potential protective effects of maternal GTE intake during lactation on HF diet-induced hepatic lipid accumulation in adult male rat offspring and the possible underlying mechanisms.

Hoarding disorder (HD) is a psychiatric condition that negatively impacts individual sufferers, their families and the larger community. The disorder goes beyond problems with excessive clutter; it also presents with deficits in executive functioning, attachment and affect regulation deficits. This paper focusses on the needs of adult children of parents with HD, who directly experience the consequences of the disorder throughout their life cycle. We explore the existing research on the psychological, relational and social impact of parental hoarding on adult offspring. We discuss the clinical implications of these findings and offer possible psychological interventions that may be of help in this vulnerable population.

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 ...

In birds that breed cooperatively in family groups, adult offspring often delay dispersal to assist the breeding pair in raising their young. Kin selection is thought to play an important role in the evolution of this breeding system. However, evidence supporting the underlying assumption that helpers increase the reproductive success of breeders is inconsistent. In 10 out of 19 species where the effect of helpers on breeder reproductive success has been estimated while controlling for the effects of breeder and territory quality, no benefits of help were detected. Here, we use phylogenetic meta-analysis to show that the inconsistent evidence for helper benefits across species is explained by study design. After accounting for low sample sizes and the different study designs used to control for breeder and territory quality, we found that helpers consistently enhanced the reproductive success of breeders. Therefore, the assumption that helpers increase breeder reproductive success is supported by evidence across cooperatively breeding birds.

Midlife is a time of both turbulence and stability for long-term romantic couples, a period that may bring adversity in the form of changed roles, distressed adult offspring, health conditions, and...

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.

Maternal immune activation (MIA) is a risk factor for schizophrenia and many of the symptoms and neurodevelopmental changes associated with this disorder have been modelled in the rodent. While several previous studies have reported that rodent ultrasonic vocalizations (USVs) are affected by MIA, no previous study has examined whether MIA affects the way that individual USVs occur over time to produce vocalisation sequences. The sequential aspect of this behaviour may be particularly important because changes in sequencing mechanisms have been proposed as a core deficit in schizophrenia. The present research generates MIA with POLY I:C administered to pregnant Sprague-Dawley rat dams at GD15. Male pairs of MIA adult offspring or pairs of their saline controls were placed into a two-chamber apparatus where they were separated from each other by a perforated plexiglass barrier. USVs were recorded for a period of 10 ​min and automated detection and call review were used to classify short call types in the nominal 50 ​kHz band of social affiliative calls. Our data show that the duration of these 50-kHz USVs is longer in MIA rat pairs and the time between calls is shorter. Furthermore, the transition probability between call pairs was different in the MIA animals compared to the control group, indicating alterations in sequential behaviour. These results provide the first evidence that USV call sequencing is altered by the MIA intervention and suggest that further investigations of these temporally extended aspects of USV production are likely to reveal useful information about the mechanisms that underlie sequence generation. This is particularly important given previous research suggesting that sequencing deficits may have a significant impact on both behaviour and cognition., Highlights • Maternal Immune Activation alters affiliative, ultrasonic vocalizations in rats. • MIA alters transition probabilities between individual calls. • Transition changes may reflect sequencing deficits in MIA animals. • Disorganized sequencing is fundamental to schizophrenia. • MIA affected vocalizations provide a new preclinical model of disorganization.

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

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.

The aim of this study was to investigate associations between maternal and paternal externalising, experiences of early life adversity (ELA), internalising and externalising in adult offspring, and the role of sex. Using data collected in wave three of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) we utilised structural equation modelling to test a hypothesised moderated mediation model associating maternal and paternal externalising, and internalising and externalising in offspring, mediated by early life adversities and moderated by sex. Our study included a total of n=26,728 participants which were randomly split into two groups and analysed separately to test whether it was possible to replicate our own results. No direct association was demonstrated between maternal externalising or paternal externalising and internalising or externalising in offspring; experiences of ELA were associated only with internalising in offspring, but not with externalising; ELA was associated with maternal externalising and paternal externalising in females only. The relationship between paternal externalising and internalising in male offspring was mediated by ELA, as was the relationship between maternal externalising and internalising in male offspring. The relationship between parental externalising and internalising in females however was not mediated by ELA. Results did not provide support for the study’s hypotheses.

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.

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.

Using novel panel data spanning 1940-2000, we examine the adult offspring of the Great Migration who returned to the South. We observe two types of return migrants: (1) southern-born, "lifetime" return migrants who were born in the South, resided outside of the South in 1940, and returned to the South by 2000, and (2) northern-born, "generational" return migrants whose parents were born in the South but who, themselves, were born in the North, resided in the North in 1940, and had returned to the South by 2000. These data also allow us to observe return migrants and their parents over a longer period of time than any previous data source, permitting us to consider the early-life predictors of return migration. We find that generational migrants comprise a sizeable segment of all second-generation return migrants to the South and that these migrants are positively selected on their own and their parents' socioeconomic characteristics, relative to the second-generation migrants who remain in the North. Conversely, southern-born, lifetime, return migrants are negatively selected. Our investigation provides a broader and more representative view of who return migrants are and illustrates the underappreciated importance of generational ties to place for migration decisions.

Parents often provide the bulk of caregiving supports for their adult offspring with intellectual and developmental disabilities (IDD). Given the longer lives of people with IDD, however, such caregiving roles may transition to siblings. Thus, it is critical to conduct future planning among family members (e.g., parents, siblings) to prepare for the transition of caregiving roles. To this end, we interviewed 10 parent-sibling dyads (N = 20) of people with IDD about long-term planning. Both parents and siblings reported family-related and systemic barriers to developing future plans. Siblings (unlike parents) reported wanting more communication among family members about planning. Implications for future research and practice are discussed.

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...

This study aims to give voice to the offspring of ‘Righteous Among the Nations’ who were children during World War II. Unlike the children of survivors and the children of perpetrators, this unique...

Emerging adulthood is a new, distinct life stage for 18- to 29-year-olds in the United States. In the sixth wave of data collection in a longitudinal cohort study (started in 1986), predictors of mental health were examined in the emerging adult offspring within lesbian-parent parent families. The donor-conceived offspring were 25 years old. In cross-sectional analyses, we assessed whether their mental health (life satisfaction and behavioral/emotional problems) was associated with personal characteristics, family characteristics, quality of important relationships, and experiences of homophobic stigmatization. The findings revealed that the predictors of mental health in these offspring were typical of what has been previously reported on emerging adults. However, offspring who reported stigmatization because of their parents' sexual identity had higher rates of behavioral/emotional problems than those who did not.

Background and aims: Pregnancy is an important period in women life regarding different aspects including physical activity which may be effective on various health indices of offspring. One of the common and expanding women diseases is breast cancer and two of its related indices are BRCA1 and P53. Thus, the aim of present study was estimating the effect of aerobic training during pregnancy in pregnant rats on the expression of BRCA1 and P53 genes of their offspring’s breast tissue. Methods: 20 female Sprague Dawley rats were randomly divided into two groups of exercise during pregnancy (T) (221±9.9) and control (C) (223.8±12.8). The aerobic exercise training was performed immediately after observation of the vaginal plaque of approving pregnancy for 21 days and 5 sessions per week with moderate intensity. About 2 to 3 days before delivery, their training program was terminated. Tissue sampling of Pairs 4, 5, and 6 of breast tissues in 8 weeks offspring rats was performed to evaluate the expression of BRCA1 and P53 gene. Data was analyzed using SPSS software and statistical tests of Shapiro-Wilk to control the distribution of data, and independent t-test for comparisons of between groups. Results: Aerobic training with moderate intensity during pregnancy increased significantly mRNA of the BRCA1 gene (P=0.001), but there was no significant change in mRNA of the P53 (P=0.69). Conclusion: Considering the effect of exercise during pregnancy on increasing BRCA1 gene expression in their offspring's and association of the gene with breast, it seems that moderate exercise during pregnancy can reduce the risk of breast cancer in children.

Background The diagnosis of intellectual disability in children can produce complex grief-related feelings in their parents. Previous studies have focused on the moment of the diagnosis or the early life of the children, and little research has been conducted on their feelings of grief in adulthood. The objective was to analyse the process of grief/loss in parents of adult offspring with intellectual disability. Method The intentional sampling included sixteen parents who responded to semi-structured interviews. A qualitative study was conducted based on grounded theory. Results Five categories were identified: "Reception of the diagnosis", "Emotional bonds with the child", "Experience of loss and feelings in response to intellectual disability diagnosis", "Recurrent grief" and "Coping strategies". Conclusions Recurring feelings of loss experienced by parents in relation to their child's diagnosis persist over time. Specialized emotional interventions are needed to help parents to reduce the intensity of their feelings of grief.

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).

Maternal obesity has significant consequences on the lifelong health of the developing child and rising global incidences make it one of the most common comorbidities during pregnancy. Offspring of obese mothers are at an increased risk of hospitalization for respiratory infections throughout childhood, which predispose these children to non-communicable respiratory diseases in later life. Animal models of maternal high fat diet (mHFD) feeding have observed common inflammatory outcomes with obesogenic models, but the effect on offspring varies with timing of the nutritional challenge and diet composition across studies. These studies demonstrate significant alterations to circulating and lung specific immune cells but the sequence of events that link maternal diet to these fetal outcomes are unclear, nor have they been tested in the context of a bacterial respiratory infection. Streptococcus pneumonaie is the most common causative pathogen of bacterial pneumonia and meningitis, making it of high clinical relevance. We aimed to investigate the effect of a mHFD (45% kcal from fat) during gestation and lactation, on offspring outcome and recovery from Streptococcus pneumoniae infection. Immunophenotyping, both before and after infection, revealed a hypo-inflammatory phenotype in circulating monocytes of the mHFD offspring with a decreased capacity to both initiate and terminate inflammatory responses. These offspring had significantly higher bacterial counts in lung tissues during infection and sustained cellular inflammation in survivors. In this thesis, we present foundational work on the detrimental influence of excess maternal nutrition on offspring immune function and infection outcomes, which may be involved in susceptibility to inflammatory and chronic disease in later life. A better understanding of this deep and lasting influence of the maternal environment will allow us to target preconception health as a form of harm reduction, informing stake holders and institutions to direct efforts towards DOHaD knowledge translation. Thesis Master of Science (MSc)

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

Background There are mixed findings in the literature regarding the association between parental alcohol communication and offspring alcohol use. To clarify this association, this study tested a prospective mediated moderation model in which the association between parental communication about the risks of alcohol use and emerging adult offspring drinking was mediated by offspring perceived parental approval of drinking. Parental alcohol expectancies and use were tested as moderators of the link between communication and perceived approval. Method The community sample of 378 emerging adult and caregiver dyads completed 3 annual assessments (first assessment mean age = 19.13). The sample was 54% female and majority White/non-Hispanic (76%). Caregivers reported on their own alcohol expectancies and use, and emerging adult offspring reported on parental communication of alcohol risks, perceived parental approval of drinking, and their own alcohol use. Multilevel modeling was used to test hypotheses. Results Mediated moderation was largely supported. More frequent communication about the risks of drinking was prospectively associated with low levels of perceived parental approval of alcohol use, which in turn was associated with low levels of offspring drinking. This pathway depended on parental alcohol expectancies. Conclusions Findings suggest that including mediators (e.g., perceived approval of drinking) helps to clarify the mixed literature on parental communication about alcohol and that parental attitudes about alcohol can impact the effectiveness with which parents convey the risk of alcohol to offspring.

Setting and objective In Italy, over the last decades, elderly care has been mostly provided by family members, especially adult offspring, and in particular daughters. This paper investigates the relationship between informal caregiving and mental distress among Italians aged 35–59, with a focus on gender effect and parenthood responsibilities. Data The dataset is the European Health Interview Survey (EHIS), second wave, year 2015. As far as it is known, the Italian EHIS has not been used for studies on ageing and caregiving. Methods Using selected subsamples, a Propensity Score Matching between caregivers and non-caregivers aged 35–59 is implemented, with the aim of measuring the difference in level of depression, if any, between the two groups. Results Findings show that women providing their frail relatives with informal care are less likely to suffer from mental distress compared to non-carers. However, results change radically if they have children aged less than 15 at home, and a higher probability of being depressed is detected for women overwhelmed by the double responsibility of assisting both dependent relatives and their own children. Results are not significant for men.

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

In aging studies, personhood has become a common lens through which to understand the multitude of aging experiences. It has been shown that conceptions of personhood predispose certain patterns of relationship, however, there is a dearth of research directly applying the framework of personhood to the study of intergenerational relations in late life. This paper explicitly examines the ways in which notions of personhood impact intergenerational relationships, specifically between village elders and their caregiving adult offspring, through an ethnographic study in a farming village in the Phenpo region of Central Tibet. Specifically, I explore how Phenpo personhood, which stresses both relationalism and individualism, is constructed. I then illustrate how these two dimensions of personhood undergird a harmonious relationship between generations that values dependency but allows room for independence. The analytic lens of personhood thus opens up new ways of investigating aging, care, and what binds generations together.