In this study, diabetes mellitus (DM) was induced in Wistar rats during pregnancy and maintained in the postpartum period (PP) and we evaluated systolic blood pressure (SBP), glomerular filtration rate (GFR) and renal immunohistochemical and morphometric studies from different groups: G1 (non-pregnant control rats), G2 (non-pregnant diabetic rats), G3 (control mothers) and G4 (diabetic mothers). We found that there were no differences in relation to SBP, but there was a tendency for reduction in GFR from G4 compared with the other groups (G). There was increased total kidney weight/body weight ratio of G4 compared with other G. There were increase in glomerular tuft area in G3 and G4 compared with G1 and G2. G2 and G4 showed even higher percentage of cortical collagen. G3 showed increased glomerular proliferating cells compared with G1 and G2, while in G4 this number was smaller than G3. Cell proliferation was higher in the tubulointerstitial (TBI) compartment from G4. Glomerular and TBI α-smooth muscle actin expression was increased in G4 compared with other G. The glomerular p-p38 expression showed a pattern similar to proliferation cell nuclear antigen, with a reduction of p-p38 in G4 relative to other G. The immunoreactivity of p-JNK was higher in both the glomeruli and TBI compartment in G4 compared with G1, G2 and G3. The DM induced during pregnancy and maintained in the PP resulted in renal structural and functional changes to mothers. In addition, altered mitogen-activated protein kinase expression in association with these changes may play an important role in renal damage observed in the present investigation.

Recent findings highlight that there are prenatal risks for affective disorders that are mediated by glucocorticoid mechanisms, and may be specific to females. There is also evidence of sex differences in prenatal programming mechanisms and developmental psychopathology, whereby effects are in opposite directions in males and females. As birth weight is a risk for affective disorders, we sought to investigate whether maternal prenatal cortisol may have sex-specific effects on fetal growth. Participants were 241 mothers selected from the Wirral Child Health and Development Study (WCHADS) cohort (n=1233) using a psychosocial risk stratifier, so that responses could be weighted back to the general population. Mothers provided saliva samples, which were assayed for cortisol, at home over 2 days at 32 weeks gestation (on waking, 30-min post-waking and during the evening). Measures of infant birth weight (corrected for gestational age) were taken from hospital records. General population estimates of associations between variables were obtained using inverse probability weights. Maternal log of the area under the curve cortisol predicted infant birth weight in a sex-dependent manner (interaction term P=0.029). There was a positive and statistically significant association between prenatal cortisol in males, and a negative association in females that was not statistically significant. A sex interaction in the same direction was evident when using the waking (P=0.015), and 30-min post-waking (P=0.013) cortisol, but not the evening measure. There was no interaction between prenatal cortisol and sex to predict gestational age. Our findings add to an emerging literature that suggests that there may be sex-specific mechanisms that underpin fetal programming.

This study was designed to explore the association between undernutrition in the growth period and cardiovascular risk factors in a middle-aged Chinese population. A total of 1756 subjects, aged 45–60 years, were invited to participate in the Hefei Nutrition and Health Study and divided into three groups according to their self-reported animal food intake in the growth period. Group 1, Group 2 and Group 3 were defined as undernutrition, nutritional improvement and the good nutrition group, respectively. In the three groups, the subjects in Groups 1 and 2 had more oil and salt intake (P<0.001), and less eggs and milk intake (P<0.001), when compared with the subjects in Group 3. After adjusting for age, education, smoking status and other confounding factors, it was found that male participants who experienced nutritional improvement before age 18 had higher risk of hypertension [odds ratio (OR)=1.68; 95% confidence intervals (CI): 1.05, 2.69] than those with good nutrition, and female participants with undernutrition (OR=1.52; 95% CI: 1.01, 2.29) and nutritional improvement (OR=1.68; 95% CI: 1.04, 2.69) before age 18 had a higher risk of hypertension than those with good nutrition. For diabetes, obesity, hypercholesterolemia and hypertriglyceridemia, our results did not found difference among the three groups both in male and female. Our findings indicated that nutritional deficiency in childhood was associated with bad dietary behaviors and a significantly increased risk of hypertension in middle age. Therefore, early adequate nutrition is very important for the prevention of non-communicable diseases later.

Polycystic ovary syndrome (PCOS) affects ~7% of reproductive age women. Although its etiology is unknown, in animals, excess prenatal testosterone (T) exposure induces PCOS-like phenotypes. While measuring fetal T in humans is infeasible, demonstrating in utero androgen exposure using a reliable newborn biomarker, anogenital distance (AGD), would provide evidence for a fetal origin of PCOS and potentially identify girls at risk. Using data from a pregnancy cohort (The Infant Development and Environment Study), we tested the novel hypothesis that infant girls born to women with PCOS have longer AGD, suggesting higher fetal T exposure, than girls born to women without PCOS. During pregnancy, women reported whether they ever had a PCOS diagnosis. After birth, infant girls underwent two AGD measurements: anofourchette distance (AGD-AF) and anoclitoral distance (AGD-AC). We fit adjusted linear regression models to examine the association between maternal PCOS and girls’ AGD. In total, 300 mother–daughter dyads had complete data and 23 mothers reported PCOS. AGD was longer in the daughters of women with a PCOS diagnosis compared with daughters of women with no diagnosis (AGD-AF: β=1.21, P=0.05; AGD-AC: β=1.05, P=0.18). Results were stronger in analyses limited to term births (AGD-AF: β=1.65, P=0.02; AGD-AC: β=1.43, P=0.09). Our study is the first to examine AGD in offspring of women with PCOS. Our results are consistent with findings that women with PCOS have longer AGD and suggest that during PCOS pregnancies, daughters may experience elevated T exposure. Identifying the underlying causes of PCOS may facilitate early identification and intervention for those at risk.

Bisphenol A (BPA) is a chemical found in plastics that resembles oestrogen in organisms. Developmental exposure to endocrine-disrupting chemicals, such as BPA, increases the susceptibility to type 2 diabetes (T2DM) and cardiovascular diseases. Animal studies have reported a nephron deficit in offspring exposed to maternal diabetes. The aim of this study was to investigate the prenatal BPA exposure effects on nephrogenesis in a mouse model that was predisposed to T2DM. This study quantitatively evaluated the renal structural changes using stereology and histomorphometry methods. The OF1 pregnant mice were treated with a vehicle or BPA (10 or 100 μg/kg/day) during days 9–16 of gestation (early nephrogenesis). The 30-day-old offspring were sacrificed, and tissue samples were collected and prepared for histopathological and stereology studies. Glomerular abnormalities and reduced glomerular formation were observed in the BPA offspring. The kidneys of the BPA10 and BPA100 female offspring had a significantly lower glomerular number and density than those of the CONTROL female offspring. The glomerular histomorphometry revealed a significant difference between the female and male CONTROL offspring for the analysed glomerular parameters that disappeared in the BPA10 and BPA100 offspring. In addition, the kidney histopathological examination showed typical male cuboidal epithelial cells of the Bowman capsule in the female BPA offspring. Exposure to environmentally relevant doses of BPA during embryonic development altered nephrogenesis. These structural changes could be associated with an increased risk of developing cardiometabolic diseases later in life.

Exposure to prenatal hypoxia in rats leads to intrauterine growth restriction (IUGR), decreases fetal cardiomyocyte proliferation and increases the risk to develop cardiovascular diseases (CVD) later in life. The tumor necrosis factor-related weak inducer of apoptosis (TWEAK) induces cardiomyocyte proliferation through activation of the fibroblast growth factor-inducible molecule 14 (Fn-14) receptor. The TWEAK/Fn-14 pathway becomes quiescent shortly after birth, however, it becomes upregulated with CVD; suggesting that it could be a link between the increased susceptibility to CVD in pregnancies complicated by hypoxia/IUGR. We hypothesized that offspring exposed to prenatal hypoxia will exhibit reduced cardiomyocyte proliferation due to reduced Fn-14 expression and that the TWEAK/Fn-14 pathway will be expressed in those adult offspring. We exposed pregnant Sprague Dawley rats to control (21% oxygen) or hypoxic (11% oxygen) conditions from gestational days 15 to 21. Ventricular cardiomyocytes were isolated from male and female, control and hypoxic offspring at postnatal day 1. Proliferation was assessed in the presence or absence of r-TWEAK (72 h, 100 ng/ml). Prenatal hypoxia was not associated with differences in Fn-14 protein expression in either male or female offspring. Cardiomyocytes from prenatal hypoxic male, but not female, offspring had decreased proliferation compared with controls. Addition of r-TWEAK increased cardiomyocyte proliferation in all offspring. In adult offspring of all groups, the TWEAK/Fn-14 pathway was not detectable. Cardiomyocyte proliferation was reduced in only male offspring exposed to prenatal hypoxia but this was not due to changes in the Fn-14 pathway. Studies addressing other pathways associated with CVD and prenatal hypoxia are needed.

Maternal stress has been linked to low birth weight in newborns. One potential pathway involves epigenetic changes at candidate genes that may mediate the effects of prenatal maternal stress on birth weight. This relationship has been documented in stress-related genes, such as NR3C1. There is less literature exploring the effect of stress on growth-related genes. IGF1 and IGF2 have been implicated in fetal growth and development, though via different mechanisms as IGF2 is under imprinting control. In this study, we tested for associations between prenatal stress, methylation of IGF1 and IGF2, and birth weight. A total of 24 mother–newborn dyads in the Democratic Republic of Congo were enrolled. Ethnographic interviews were conducted with mothers at delivery to gather culturally relevant war-related and chronic stressors. DNA methylation data were generated from maternal venous, cord blood and placental tissue samples. Multivariate regressions were used to test for associations between stress measures, DNA methylation and birth weight in each of the three tissue types. We found an association between IGF2 methylation in maternal blood and birth weight. Previous literature on the relationship between IGF2 methylation and birth weight has focused on methylation at known differentially methylated regions in cord blood or placental samples. Our findings indicate there may be links between the maternal epigenome and low birth weight that rely on mechanisms outside known imprinting pathways. It thus may be important to consider the effect of maternal exposures and epigenetic profiles on birth weight even in the setting of maternally imprinted genes such as IGF2.

This study investigates relations of maternal N-3 and N-6 polyunsaturated fatty acids (PUFA) intake during pregnancy with offspring body mass index (BMI), height z-score and metabolic risk (fasting glucose, C-peptide, leptin, lipid profile) during peripuberty (8–14 years) among 236 mother–child pairs in Mexico. We used food frequency questionnaire data to quantify trimester-specific intake of N-3 alpha-linolenic acid, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA); N-6 linoleic acid and arachidonic acid (AA); and N-6:N-3 (AA:EPA+DHA), which accounts for the fact that the two PUFA families have opposing effects on physiology. Next, we used multivariable linear regression models that accounted for maternal education and parity, and child’s age, sex and pubertal status, to examine associations of PUFA intake with the offspring outcomes. In models where BMI z-score was the outcome, we also adjusted for height z-score. We found that higher second trimester intake of EPA, DHA and AA were associated with lower offspring BMI and height z-score. For example, each 1-s.d. increment in second trimester EPA intake corresponded with 0.25 (95% CI: 0.03, 0.47) z-scores lower BMI and 0.20 (0.05, 0.36) z-scores lower height. Accounting for height z-score in models where BMI z-score was the outcome attenuated estimates [e.g., EPA: −0.16 (−0.37, 0.05)], suggesting that this relationship was driven by slower linear growth rather than excess adiposity. Maternal PUFA intake was not associated with the offspring metabolic biomarkers. Our findings suggest that higher PUFA intake during mid-pregnancy is associated with lower attained height in offspring during peripuberty. Additional research is needed to elucidate mechanisms and to confirm findings in other populations.

Intrauterine growth restriction (IUGR) and fetal exposure to a maternal high-fat diet (HFD) independently increase the risk of developing obesity in adulthood. Excess glucocorticoids increase obesity. We hypothesized that surgically induced IUGR combined with an HFD would increase adiposity and glucocorticoids more than in non-IUGR offspring combined with the same HFD, findings that would persist despite weaning to a regular diet. Non-IUGR (N) and IUGR (I) rat offspring from dams fed either regular rat chow (R) or an HFD (H) were weaned to either a regular rat chow or an HFD. For non-IUGR and IUGR rats, this study design resulted in three diet groups: offspring from dams fed a regular diet and weaned to a regular diet (NRR and IRR), offspring rats from dams fed an HFD and weaned to a regular diet (NHR and IHR) and offspring from dams fed an HFD and weaned to an HFD (NHH and IHH). Magnetic resonance imaging or fasting visceral and subcutaneous adipose tissue collection occurred at postnatal day 60. IHH male rats had greater adiposity than NHH males, findings that were only partly normalized by weaning to a regular chow. IHH male rats had a 10-fold increase in serum corticosterone levels. IHH female rats had increased adiposity and serum triglycerides. We conclude that IUGR combined with an HFD throughout life increased adiposity, glucocorticoids and triglycerides in a sex-specific manner. Our data suggest that one mechanism through which the perinatal environment programs increased adiposity in IHH male rats may be via increased systemic glucocorticoids.

Exposure to maternal over-nutrition in utero is linked with developmental programming of obesity, metabolic syndrome and cardiovascular disease in offspring, which may be exacerbated by postnatal high-fat (HF) diet. Skeletal muscle mitochondrial function contributes to substrate metabolism and is impaired in metabolic disease. We examined muscle mitochondrial respiration in male and female mice exposed to maternal HF diet in utero, followed by postweaning HF diet until middle age. After in utero exposure to maternal control (Con) or HF diet (45% kcal fat; 39.4% lard, 5.5% soybean oil), offspring were weaned to Con or HF, creating four groups: Con/Con (male/female (m/f), n=8/8), Con/HF (m/f, n=7/4), HF/Con (m/f, n=9/6) and HF/HF (m/f, n=4/4). Oxidative phosphorylation (OXPHOS) and electron transfer system (ETS) capacity were measured in permeabilized gastrocnemius bundles. Maternal HF diet increased fasting glucose and lean body mass in males and body fat percentage in both sexes (P⩽0.05). Maximal adenosine diphosphate-stimulated respiration (complex I OXPHOS) was decreased by maternal HF diet in female offspring (−21%, P=0.053), but not in male (−0%, P>0.05). Sexually divergent responses were exacerbated in offspring weaned to HF diet. In females, OXPHOS capacity was lower (−28%, P=0.041) when weaned to high-fat (HF/HF) v. control diet (HF/Con). In males, OXPHOS (+33%, P=0.009) and ETS (+42%, P=0.016) capacity increased. Our data suggest that maternal lard-based HF diet, rich in saturated fat, affects offspring skeletal muscle respiration in a sex-dependent manner, and these differences are exacerbated by HF diet in adulthood.

There is an increasing incidence of overweight/obesity and mental health disorders in young adults and the two conditions often coexist. We aimed to investigate the influence of antenatal and postnatal factors that may underlie this association with a focus on maternal prenatal smoking, socio-economic status and gender. Data from the Western Australian Pregnancy Cohort (Raine) Study (women enrolled 1989–1991) including 1056 offspring aged 20 years (cohort recalled 2010–2012) were analyzed (2015–2016) using multivariable models for associations between offspring depression scores (DASS-21 Depression-scale) and body mass index (BMI), adjusting for pregnancy and early life factors and offspring behaviours. There was a significant positive relationship between offspring depression-score and BMI independent of gender and other psychosocial covariates. There was a significant interaction between maternal prenatal smoking and depression-score (interaction coefficient=0.096; 95% CI: 0.006, 0.19, P=0.037), indicating the relationship between depression-score and BMI differed according to maternal prenatal smoking status. In offspring of maternal prenatal smokers, a positive association between BMI and depression-score (coefficient=0.133; 95% CI: 0.05, 0.21, P=0.001) equated to 1.1 kg/m2 increase in BMI for every 1standard deviation (8 units) increase in depression-score. Substituting low family income during pregnancy for maternal prenatal smoking in the interaction (interaction coefficient=0.091; 95% CI: 0.01, 0.17, P=0.027) showed a positive association between BMI and depression score only among offspring of mothers with a low family income during pregnancy (coefficient=0.118; 95% CI: 0.06, 0.18, P<0.001). There were no significant effects of gender on these associations. Whilst further studies are needed to determine whether these associations are supported in other populations, they suggest potentially important maternal behavioural and socio-economic factors that identify individuals vulnerable to the coexistence of obesity and depression in early adulthood.

Diverse environmental conditions surrounding preimplantation embryos, including available nutrients, affect their metabolism and development in both short- and long-term manner. Thioredoxin-interacting protein (TXNIP) is a possible marker for preimplantation stress that is implicated in in vitro fertilization- (IVF) induced long-term DOHaD effects. B vitamins, as participants in one-carbon metabolism, may affect preimplantation embryos by epigenetic alterations of metabolically and developmentally important genes. In vitro-produced bovine embryos were cultured with or without Roswell Park Memorial Institute 1640 vitamin mixture, containing B vitamins and B vitamin-like substances, from day 3 after IVF and we evaluated blastocyst development and TXNIP messenger RNA (mRNA) expression in the blastocysts by reverse transcription-quantitative polymerase chain reaction. The degree of trimethylation of histone H3 lysine 27 (H3K27me3) at TXNIP promoter was examined semi-quantitatively by chromatin immunoprecipitation polymerase chain reaction. Total H3K27me3 were also compared between the groups by Western blot analysis. The vitamin treatment significantly increased the rates of blastocyst development (P<0.05) and their hatching (P<0.001) from the zona pellucida by day 8. The mRNA expression of TXNIP was lower (P<0.01) in blastocysts in the vitamin-mixture-treated group concomitant with higher (P<0.05) level of H3K27me3 of its promoter compared with the control group. The total H3K27me3 in the vitamin-mixture-treated group was also higher (P<0.01) than that in the control group. The epigenetic control of genes related to important metabolic processes during the periconceptional period by nutritional conditions in utero and/or in vitro may have possible implication for the developmental programming during this period that may impact the welfare and production traits of farm animals.

In utero exposure to the ubiquitous plasticizer, bisphenol A (BPA) is associated with offspring obesity. As adipogenesis is a critical factor contributing to obesity, we determined the effects of in vivo maternal BPA and in vitro BPA exposure on newborn adipose tissue at the stem-cell level. For in vivo studies, female rats received BPA before and during pregnancy and lactation via drinking water, and offspring were studied for measures of adiposity signals. For in vitro BPA exposure, primary pre-adipocyte cell cultures from healthy newborns were utilized. We studied pre-adipocyte proliferative and differentiation effects of BPA and explored putative signal factors which partly explain adipose responses and underlying epigenetic mechanisms mediated by BPA. Maternal BPA-induced offspring adiposity, hypertrophic adipocytes and increased adipose tissue protein expression of pro-adipogenic and lipogenic factors. Consistent with in vivo data, in vitro BPA exposure induced a dose-dependent increase in pre-adipocyte proliferation and increased adipocyte lipid content. In vivo and in vitro BPA exposure promotes the proliferation and differentiation of adipocytes, contributing to an enhanced capacity for lipid storage. These findings reinforce the marked effects of BPA on adipogenesis and highlight the susceptibility of stem-cell populations during early life with long-term consequence on metabolic homeostasis.

There is strong evidence that physical activity (PA) has an influence on physical performance in later life. Also, a small body size at birth has been associated with lower physical functioning in older age and both small and high birth weight have shown to be associated with lower leisure time physical activity. However, it is unknown whether size at birth modulates the association between PA and physical performance in old age. We examined 695 individuals from the Helsinki Birth Cohort Study born in Helsinki, Finland between 1934 and 1944. At a mean age of 70.7 years PA was objectively assessed with a multisensory activity monitor and physical performance with the Senior Fitness Test (SFT). Information on birth weight and gestational age was retrieved from hospital birth records. The study participants were divided in three birth weight groups, that is <3000 g, 3000–3499 g and ⩾3500 g. The volume of PA was significantly associated with the physical performance in all birth weight groups. However, the effect size of the association was large and significant only in men with a birth weight <3000 g (β 0.59; 95% confidence interval 0.37–0.81, P<0.001). Our study shows that the association between PA and physical performance is largest in men with low birth weight. Our results suggest that men with low birth weight might benefit most from engaging in PA in order to maintain a better physical performance.

Alcohol consumption around the time of conception is highly prevalent in Western countries. Exposure to ethanol levels during gestation has been associated with altered development of the mesolimbic reward pathway in rats and increased propensity to addiction, however the effect of exposure only around the time of conception is unknown. The current study investigated the effects of periconceptional alcohol exposure (PC:EtOH) on alcohol and palatable food preferences and gene expression in the ventral tegmental area (VTA) and the nucleus accumbens of the adult offspring. Rats were exposed to a liquid diet containing ethanol (EtOH) (12.5% vol/vol) or a control diet from 4 days before mating until 4 days after mating. PC:EtOH had no effect on alcohol preference in either sex. At 15 months of age, however, male PC:EtOH offspring consumed more high-fat food when compared with male control offspring, but this preference was not observed in females. Expression of the dopamine receptor type 1 (Drd1a) was lower in the VTA of male PC:EtOH offspring compared with their control counterparts. There was no effect of PC:EtOH on mRNA expression of the µ-opioid receptor, tyrosine hydroxylase (Th), dopamine receptor type 2 (Drd2) or dopamine active transporter (Slc6a3). These data support the hypothesis that periconceptional alcohol exposure can alter expression of key components of the mesolimbic reward pathway and heighten the preference of offspring for palatable foods and may therefore increase their propensity towards diet-induced obesity. These results highlight the importance of alcohol avoidance when planning a pregnancy.

This study, carried out in two Italian Institutions, assesses the frequency of 27 potential autism risk factors related to pregnancy and peri- and postnatal periods by interviewing mothers who had children with autism, children with autism and one or two typically developing siblings, or only typically developing children. The clinical sample included three case groups: 73 children and adolescents with autism (Group A), 35 children and adolescents with autism (Group A1) having 45 siblings (Group B) and 96 typically developing children (Group C) matched for gender and age. Twenty-five out of 27 of risk factors presented a higher frequency in Group A in comparison with Group C and for nine of them a statistically significant difference was found. Twenty-one out of 27 of risk factors presented a higher frequency in Group A in comparison with Group B. A higher prevalence of environmental risk factors was observed in 11 risk factors in the Group A1 in comparison with Group B and for nine of them an odds ratio higher than 1.5 was found. For 13 factors there was a progressive increase in frequency going from Group C, B and A and a statistically higher prevalence of the mean number of stressful events per pregnancy was recorded in Group A when compared with Groups B and C. The results suggest that environmental, incidental phenomena and stressful life events can influence pregnancy outcome in predisposed subjects, pointing out a possible threshold effect in women who are predisposed to have suboptimal pregnancies.

Intrauterine environmental factors can be associated with perinatal complications and long-term health outcomes although the underlying mechanisms remain poorly defined. Meconium formed exclusively in utero and passed naturally by a neonate may contain proteins which characterise the intrauterine environment. The aim of the study was proteomic analysis of the composition of meconium proteins and their classification by biological function. Proteomic techniques combining isoelectrofocussing fractionation and LC-MS/MS analysis were used to study the protein composition of a meconium sample obtained by pooling 50 serial meconium portions from 10 healthy full-term neonates. The proteins were classified by function based on the literature search for each protein in the PubMed database. A total of 946 proteins were identified in the meconium, including 430 proteins represented by two or more peptides. When the proteins were classified by their biological function the following were identified: immunoglobulin fragments and enzymatic, neutrophil-derived, structural and fetal intestine-specific proteins. Meconium is a rich source of proteins deposited in the fetal intestine during its development in utero. A better understanding of their specific biological functions in the intrauterine environment may help to identify these proteins which may serve as biomarkers associated with specific clinical conditions/diseases with the possible impact on the fetal development and further health consequences in infants, older children and adults.

Clinical depression is accompanied by changes in sleep patterning, which is controlled in a circadian fashion. It is thus desirable that animal models of depression mirror such diurnally-specific state alterations, along with other behavioral and physiological changes. We previously found several changes in behavior indicative of a depression-like phenotype in offspring of rats subjected to repeated, variable prenatal stress (PNS), including increased locomotor activity during specific periods of the circadian cycle. We, therefore, investigated whether PNS rats also exhibit alterations in sleep/wakefulness behavior around the change from light-to-dark phase. Control and PNS Sprague–Dawley rats were implanted with electrodes for continuous monitoring of electroencephalic activity used to determine behavioral state. The distribution of slow-wave sleep (SWS), rapid eye movement sleep (REMS) and wakefulness was compared for periods before and after lights were turned off, between baseline conditions and after exposure to an acute stressor. Both REMS and SWS amounts were increased in PNS rats relative to control animals in the beginning of the dark phase. REMS changes were due to an increase in REMS bout number, rather than in bout duration. During this circadian time period, we did not find any sex differences in the state changes. These results indicate that PNS affects baseline sleep patterning in both male and female rats around active-phase onset.

The study aimed to evaluate the consequences of the consumption of a high-fructose diet (HFR; fructose was responsible for 45% of the energy from carbohydrates) by the mother, the father, or both on C57BL/6 adult male offspring. Non-consanguineous parents received the diet (HFR or control, C) from 8 weeks before mating until weaning (n=10 fathers and n=10 mothers on each diet). After weaning, only the C diet was offered to offspring. The groups were formed by one male randomly taken from each litter. The offspring groups were identified according to the mother’s diet (the first letter), then the father’s diet (the second letter), that is, C/C, C/HFR, HFR/C, HFR/HFR (n=10 per group). The parents exhibited the following characteristics: compared with those of the C group, the HFR parents had higher blood pressure (BP), enlarged liver, increased hepatic triacylglycerol content, hypercholesterolemia, hypertriglyceridemia, high plasma leptin and low adiponectin. The offspring exhibited the following characteristics: compared with the C/C group, the HFR/HFR group had high BP. The C/HFR, HFR/C and HFR/HFR showed elevated uric acid and leptin levels and diminished adiponectin. The HFR/HFR group showed liver inflammation (increased NFκB, SOCS3, JNK, TNF-α, IL1-β and IL6 levels). Likewise, SREBP-1c and FAS were upregulated. In conclusion, the consumption of a HFR by the mother and/or father is associated with adverse effects on liver metabolism in adult male offspring. When both mother and father are fed a HFR, the adverse effects on the offspring are more severe.