Adult Male Rat Offspring Research Articles

Targeting on Gut Microbiota-Derived Metabolite Trimethylamine to Protect Adult Male Rat Offspring against Hypertension Programmed by Combined Maternal High-Fructose Intake and Dioxin Exposure.

Gut microbiota-dependent metabolites, in particular trimethylamine (TMA), are linked to hypertension. Maternal 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure or consumption of food high in fructose (HFR) can induce hypertension in adult offspring. We examined whether 3,3-maternal dimethyl-1-butanol (DMB, an inhibitor of TMA formation) therapy can protect adult offspring against hypertension arising from combined HFR and TCDD exposure. Pregnant Sprague–Dawley rats received regular chow or chow supplemented with fructose (60% diet by weight) throughout pregnancy and lactation. Additionally, the pregnant dams received TCDD (200 ng/kg BW orally) or a corn oil vehicle on days 14 and 21 of gestation, and days 7 and 14 after birth. Some mother rats received 1% DMB in their drinking water throughout pregnancy and lactation. Six groups of male offspring were studied (n = 8 for each group): regular chow (CV), high-fructose diet (HFR), regular diet+TCDD exposure (CT), HFR+TCDD exposure (HRT), high-fructose diet+DMB treatment (HRD), and HFR+TCDD+DMB treatment (HRTD). Our data showed that TCDD exacerbates HFR-induced elevation of blood pressure in male adult offspring, which was prevented by maternal DMB administration. We observed that different maternal insults induced distinct enterotypes in adult offspring. The beneficial effects of DMB are related to alterations of gut microbiota, the increase in nitric oxide (NO) bioavailability, the balance of the renin-angiotensin system, and antagonization of aryl hydrocarbon receptor (AHR) signaling. Our findings cast new light on the role of early intervention targeting of the gut microbiota-dependent metabolite TMA, which may allow us to prevent the development of hypertension programmed by maternal excessive fructose intake and environmental dioxin exposure.

Maternal Immune Activation Sensitizes Male Offspring Rats to Lipopolysaccharide-Induced Microglial Deficits Involving the Dysfunction of CD200-CD200R and CX3CL1-CX3CR1 Systems.

Early life challenges resulting from maternal immune activation (MIA) may exert persistent effects on the offspring, including the development of psychiatric disorders, such as schizophrenia. Recent evidence has suggested that the adverse effects of MIA may be mediated by neuron–microglia crosstalk, particularly CX3CL1–CX3CR1 and CD200–CD200R dyads. Therefore, the present study assessed the behavioural parameters resembling schizophrenia-like symptoms in the adult male offspring of Sprague-Dawley rats that were exposed to MIA and to an additional acute lipopolysaccharide (LPS) challenge in adulthood, according to the “two-hit” hypothesis of schizophrenia. Simultaneously, we aimed to clarify the role of the CX3CL1–CX3CR1 and CD200–CD200R axes and microglial reactivity in the brains of adult offspring subjected to MIA and the “second hit” wit LPS. In the present study, MIA generated a range of behavioural changes in the adult male offspring, including increased exploratory activity and anxiety-like behaviours. The most intriguing finding was observed in the prepulse inhibition (PPI) test, where the deficit in the sensorimotor gating was age-dependent and present only in part of the rats. We were able to distinguish the occurrence of two groups: responsive and non-responsive (without the deficit). Concurrently, based on the results of the biochemical studies, MIA disrupted mainly the CD200–CD200R system, while the changes of the CX3CL1–CX3CR1 axis were less evident in the frontal cortex of adult non-responsive offspring. MIA markedly affected the immune regulators of the CD200–CD200R pathway as we observed an increase in cortical IL-6 release in the responsive group and IL-4 in the non-responsive offspring. Importantly, the “second hit” generated disturbances at the behavioural and biochemical levels mostly in the non-responsive adult animals. Those offspring were characterized both by disturbed PPI and “priming” microglia. Altogether, the exposure to MIA altered the immunomodulatory mechanisms, including the CD200–CD200R axis, in the brain and sensitized animals to subsequent immunological challenges, leading to the manifestation of schizophrenia-like alterations.

Front Cover: Prenatal High‐Salt Diet–Induced Metabolic Disorders via Decreasing Peroxisome Proliferator–Activated Receptor Gamma Coactivator 1α in Adult Male Rat Offspring

Front Cover: Prenatal High‐Salt Diet–Induced Metabolic Disorders via Decreasing Peroxisome Proliferator–Activated Receptor Gamma Coactivator 1α in Adult Male Rat Offspring

Protective effect of maternal exercise against amyloid-β neurotoxicity in the male rat offspring's cerebellum.

The Developmental Origins of Health and Disease (DOHaD) states that intrauterine maternal environment influences postnatal life by programming offspring's metabolism. Intrauterine milieu induced by exercise during pregnancy promotes long-lasting benefits to the offspring's health and seems to offer some resistance against chronic diseases in adult life. Alzheimer's disease is a public health concern with limited treatment options. In the present study, we assessed the potential of maternal exercise during pregnancy in long-term programming of young adult male rat offspring's cerebellar metabolism in conferring neuroprotection against amyloid-β (Aβ) neurotoxicity. Female Wistar rats were submitted to a swimming protocol 1 week prior mating and throughout pregnancy (five sessions/a week lasting 30 min). Aβ oligomers were infused bilaterally in the brain ventricles of 60-day-old male offspring. Fourteen days after surgery, we measured parameters related to redox state, mitochondrial function, and the immunocontent of proteins related to synaptic function. We found that maternal exercise during pregnancy attenuated several parameters in the offspring's male rat cerebellum, such as the reactive species rise, the increase of inducible nitric oxide synthase immunocontent and tau phosphorylation induced by Aβ oligomers, increased mitochondrial fission indicated by dynamin-related protein 1 (DRP1), and protein oxidation identified by carbonylation. Strikingly, we find that maternal exercise promotes changes in the rat offspring's cerebellum that are still evident in young adult life. These favorable neurochemical changes in offspring's cerebellum induced by maternal exercise may contribute to a protective phenotype against Aβ-induced neurotoxicity in young adult male rat offspring.

Prenatal High-Salt Diet-Induced Metabolic Disorders via Decreasing Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1α in Adult Male Rat Offspring.

Although prenatal high-salt (HS) intake leads to physiological complications in the offspring, little is known regarding its effects on the offspring's glucose metabolism. Therefore, the objectives of this study are to determine the consequences of prenatal HS diet on the offspring's metabolism and to test a potential therapy. Pregnant rats are fed either a normal-salt (1% NaCl) or high-salt (8% NaCl) diet during the whole pregnancy. Experiments are conducted in five-month-old male offspring. It is found that the prenatal HS diet reduced the glucose tolerance and insulin sensitivity of the offspring. Additionally, there is down-regulation of peroxisome proliferator-activated receptor gamma coactivator 1 alpha (Ppargc1a/PPARGC1A) at the transcript and protein level, which leads to decreased mitochondrial biogenesis and oxidative respiration in skeletal muscle. Moreover, the down-regulation of Ppargc1a is accompanied by decreases in the expression of glucose transporter type 4 (Glut4). With endurance exercise training, these changes are mitigated, which ultimately resulted in improved insulin resistance. These findings suggest that prenatal HS intake induces metabolic disorders via the decreased expression of Ppargc1a in the skeletal muscle of adult offspring, providing novel information concerning the mechanisms and early prevention of metabolic diseases of fetal origins.

Programming of a developmental imbalance in hypothalamic glutamatergic/GABAergic afferents mediates low basal activity of the hypothalamic-pituitary-adrenal axis induced by prenatal dexamethasone exposure in male offspring rats

This study was intended to demonstrate that prenatal dexamethasone exposure (PDE) can induce low basal activity of the hypothalamic-pituitary-adrenal axis (HPAA) in male offspring rats and explore the underlying mechanism. Pregnant rats were subcutaneously administered 0.2 mg/kg/d dexamethasone from gestational day (GD) 9 to GD20. Male GD20 fetuses and postnatal day 85 adult male offspring rats were sacrificed under anesthesia. Hypothalamic cells were from GD20∼postnatal day (PD) 7 fetal male rats, treated with different concentrations of dexamethasone and the glucocorticoid receptor (GR) antagonist mifepristone for 5 days. The results suggested that dexamethasone enhanced the expression of hypothalamic L-glutamic acid decarboxylase (GAD) 67 by activating GR, further stimulating the conversion of glutamate to gamma-aminobutyric acid (GABA) and inducing an imbalance in glutamatergic/GABAergic afferents in the hypothalamic paraventricular nucleus (PVN). This imbalance change was maintained postnatally, leading to the inhibition of parvocellular neurons, and mediating the low basal activity of the HPAA in PDE offspring rats, which was manifested by decreased levels of blood adrenocorticotropic hormone and corticosterone as well as reduced expression levels of corticotrophin-releasing hormone (CRH) and arginine vasopressin (AVP) in the hypothalamus. Programming of a developmental imbalance in glutamatergic/GABAergic afferents in the PVN is a potential mechanism responsible for low basal activity of the HPAA in male PDE rats.

Effect of electronic cigarette aerosol exposure during gestation and lactation on learning and memory of adult male offspring rats

IntroductionElectronic cigarette (ECIG) use has increased worldwide, including among pregnant and breastfeeding women. In this study, we examined the effect of ECIG aerosol exposure during gestation and lactation on learning and memory of adult male offspring rats. MethodsRats were exposed to either fresh air or ECIG aerosol for one hour daily during gestational period as well as days 4–21 of lactation. Male offspring were followed through 19 weeks and then spatial learning and memory were tested by radial arm water maze (RAWM). The hippocampus was examined for biomarkers of harm, including oxidative stress, superoxide dismutase, catalase, glutathione peroxidase and thiobarbituric acid reactive substances and brain derived neurotrophic factor (BDNF). ResultsRelative to exposure to fresh air, exposure to ECIG aerosol during gestation/lactation impaired long-term memory in adult offspring (P < 0.05). This impairment was associated with increased activity of superoxide dismutase in the hippocampus (P < 0.05). BDNF and the other tested oxidative stress biomarkers were not affected by ECIG aerosol exposure (p > 0.05). ConclusionsIn conclusion, ECIG aerosol exposure during gestation and lactation impaired long-term memory and increased the activity of superoxide dismutase in the hippocampus of offspring adult rats. These results support the development of strategies to enhance ECIG cessation during pregnancy and breastfeeding.

Perinatal nicotine exposure alters miR‐181a‐mediated signaling leading to gender‐dependent development of cardiac ischemia‐sensitive phenotype in adult male offspring

Back groundCigarette smoking/nicotine exposure during pregnancy is one of the major perinatal insults resulting in an increased risk of cardiovascular diseases in offspring. However, the fetal nicotine exposure‐induced programming of adult cardiovascular dysfunction remains largely elusive. The present study tested the hypothesis that perinatal nicotine exposure caused gender‐dependent increase in heart vulnerability to ischemia‐reperfusion injury and cardiac dysfunction in adult male rat offspring through up‐regulation of miRNA‐181a (miR‐181a)‐mediated signaling pathway.MethodsNicotine or saline was administered to pregnant rats via subcutaneous osmotic minipumps from gestational day 4 until postnatal day 10. The adult (~ 3 month old) offspring were treated with miR‐181a antisense (LNA‐miR‐181a) (10 mg/kg × 2 every 5 day, i.p.) or saline. After 10 days of treatment, the rats underwent the cardiac ischemia/reperfusion (I/R) procedure and echocardiography analysis, and the left ventricle (LV) tissues were isolated for molecular biological studies.ResultsPerinatal nicotine exposure enhanced I/R‐induced cardiac infraction and dysfunction in adult male but not in female offspring. The miR‐181a levels in LV tissues were significantly higher in the nicotine‐treated group than the saline control group. In addition, nicotine exposure decreased global DNA methylation levels but enhanced AT1 and AT2 receptor protein expression, and ROS production in LV tissues in the male offspring. Furthermore, the nicotine exposure up‐regulated autophagy‐related proteins (Atg‐5, beclin‐1, LC3 II) expressions as compared to controls in the male offspring. The most importance, treatment with LNA‐miR‐181a reversed nicotine‐mediated I/R‐induced cardiac infarction and dysfunction in male offspring, which was associated with an elimination of the nicotine’s effects on miR‐181a expression, DNA methylation, AT1R/AT2R protein, ROS, and autophagy‐related proteins expressions in the male offspring.ConclusionOur data demonstrated that perinatal nicotine exposure could cause a gender‐dependent fetal programing of adult heart ischemia‐sensitive phenotype. Our findings further suggest that miR‐181a plays a casual role in nicotine‐mediated up‐regulation of oxidative stress, renin‐angiotensin system (RAS) and autophagic flux, which may contribute to the development of ischemia‐sensitive phenotype in adult male rats.Support or Funding InformationSupported in part by the NIH grants: R01HL135623, R03DA041492, and R01HD088039; TRDRP grants: 29IR0437 and T30FT0936

Maternal conjugated linoleic acid consumption prevented TAG alterations induced by a high-fat diet in male adult rat offspring.

Maternal nutritional programming by a high-fat (HF) diet is related to hepatic lipid accumulation and steatosis in offspring. Conjugated linoleic acid (CLA) might ameliorate impaired hepatic lipid homoeostasis; therefore, the aim was to investigate the potential preventive effect of maternal CLA consumption on TAG metabolism alterations induced by HF diets in adult male rat offspring receiving or not receiving CLA. Female Wistar rats were fed a control (C) diet, HF diet or HF diet supplemented with CLA (HF+CLA) for 4 weeks before mating and throughout pregnancy and lactation. After weaning, for 9 weeks, male offspring of C or HF rats continued with the same diets as their mothers (C/C or HF/HF groups, respectively) and male offspring of HF+CLA rats were fed HF or HF+CLA diets (HF+CLA/HF or HF+CLA/HF+CLA groups, respectively). Nutritional parameters, serum and liver TAG levels, the TAG secretion rate (TAG-SR) and the activities as well as gene expression of key hepatic enzymes involved in TAG regulation were assessed. The most interesting results were that maternal CLA decreased epididymal white adipose tissue weight and prevented serum and liver TAG accumulation induced by a HF diet in adult male offspring receiving or not receiving CLA. The prevention of liver steatosis in HF+CLA/HF+CLA and HF+CLA/HF offspring was associated with an increased hepatic TAG-SR. Overall, this study provides evidence that maternal CLA consumption programmes TAG regulation and in this way contributes to lowering lipid levels in tissues and preventing liver steatosis in particular.

MiR-148a/LDLR mediates hypercholesterolemia induced by prenatal dexamethasone exposure in male offspring rats

Epidemiology suggests that adverse environmental exposure during pregnancy may predispose children to hypercholesterolemia in adulthood. This study aimed to demonstrate hypercholesterolemia induced by prenatal dexamethasone exposure (PDE) in adult male offspring rats and explore the intrauterine programming mechanisms. Pregnant Wistar rats were injected subcutaneously with dexamethasone (0, 0.1, 0.2, and 0.4 mg/kg∙d) from gestational days (GD) 9 to 21, and the serum and liver of the male offsprings were collected at GD21, postnatal week (PW) 12 and 28. Furthermore, the effects of dexamethasone on the expression of low-density lipoprotein receptor (LDLR) and its epigenetic mechanism was confirmed in the bone marrow mesenchymal stem cells (BMSCs) hepatoid differentiated cells and continuous hepatocyte line. PDE could reduce the birth weight of male offsprings, increase the serum total cholesterol (TCH) level in adult rats, and decrease the liver low-density lipoprotein receptor (LDLR) expression. Serum TCH level and liver LDLR expression were decreased in PDE male fetuses in utero (GD21). Moreover, PDE increased the translocation of the glucocorticoid receptor (GR) in the fetal liver, the expression of DiGeorge syndrome critical region 8 gene (DGCR8), the pre- and post-natal expression of miR-148a. The results of PDE offspring in vivo and in vitro exhibited similar changes. These changes could be reversed by overexpressing LDLR, inhibiting miR-148a or GR. PDE caused hypercholesterolemia in male adult offspring rats, which was mediated via dexamethasone activated intrauterine hepatic GR, enhanced the expression of DGCR8 and miR-148a, thereby reducing the expression of LDLR, leading to impaired liver cholesterol reverse transport function, and finally causing hypercholesterolemia in adult rats.

Gestational Diabetes Triggers Oxidative Stress in Hippocampus and Cerebral Cortex and Cognitive Behavior Modifications in Rat Offspring: Age- and Sex-Dependent Effects.

Gestational diabetes (GD) has been linked with an increased risk of developing metabolic disorders and behavioral abnormalities in the offspring. Oxidative stress is strongly associated with neurodegeneration and cognitive disruption. In the offspring brains in a GD experimental rat model, increased oxidative stress in the prenatal and postnatal stages was reported. However, long-term alterations to offspring behavior and oxidative stress, caused by changes in the cerebral cortex and hippocampus, remain unclear. In this study, we evaluated the effect of GD on young and adult male and female rat offspring in metabolic parameters, cognitive behavior, and oxidative stress. GD was induced using streptozotocin in dams. Next, the offspring were evaluated at two and six months of age. Anxiety-like behavior was evaluated using the elevated plus maze and open field maze; spatial learning and short-term memory were evaluated using the Morris water maze and radial maze, respectively. We determined oxidative stress biomarkers (reactive oxygen species (ROS), lipid peroxidation and glutathione status) and antioxidant enzymes (superoxide dismutase and catalase) in the brain of offspring. We observed that male GD offspring showed a reduced level of anxiety at both ages as they spent less time in the closed arms of the elevated plus maze at adult age ((P = 0.019, d = 1.083 ( size effect)) and spent more time in the open area of an open field (P = 0.0412, d = 0.743) when young and adult age (P = 0.018, d = 0.65). Adult female GD offspring showed a reduced level of anxiety (P = 0.036; d = 0.966), and young female GD offspring showed a deficiency in spatial learning (P = 0.0291 vs. control, d = 3.207). Adult male GD offspring showed a deficiency in short-term memory (P = 0.017, d = 1.795). We found an increase in ROS and lipid peroxidation, a disruption in the glutathione status, and decreased activity of catalase and superoxide dismutase (P < 0.05 vs. control, d > 1.0), in the cerebral cortex and hippocampus of male and female GD offspring. GD altered metabolism; male offspring of both ages and adult females showed a high level of triglycerides and a lower level of high-density lipoprotein-cholesterol (P < 0.05 vs. control, d > 1.0). Young and adult female offspring displayed higher insulin levels (P < 0.05, d > 1.0). These results suggest that gestational diabetes modifies oxidative stress and cognitive behavior in an age- and sex-dependent manner.

Intra-uterine growth restriction induced by maternal low-protein diet causes long-term alterations of thymic structure and function in adult male rat offspring.

Early malnutrition, the first environmental cause of intra-uterine growth restriction, impairs development of the thymus. Alterations of the thymic structure and function are reported at young ages in murine and ovine models. However, descriptions of thymic consequences of fetal malnutrition at adulthood are scarce. The present study investigates thymic structure, protein expression and cell selection process observed at postnatal day 180 (PND180) in male offspring of rats exposed to maternal low-protein diet (mLPD) compared with control diet during gestation. The thymic index was lower in adult offspring exposed to mLPD (P<0·05). The thymic cortico-medullar ratio was lower in adult offspring exposed to mLPD (P<0·05). At PND180, the protein expression of the lymphotoxin β receptor (P<0·05), the autoimmune regulator (P<0·05) and Forkhead Box P3 (FoxP3; P<0·05) was all significantly lower in the mLPD group. The CD4+:CD8+ single-positive thymocyte subpopulation ratio and CD4+:CD8+ lymphocyte subpopulation ratio were increased in the mLPD group (P<0·05). Among CD3+ lymphocytes, the proportions of CD4+CD8+ double-positive lymphocytes, CD31+ recent thymic emigrants and CD4+FoxP3+ lymphocytes were not significantly different between mLPD and control groups. These findings suggest mLPD during gestation induced long-lasting alterations in the development of thymic structure and thymic cell maturation and selection process in adult male rat offspring.

Resilience to acute kidney injury in offspring of maternal protein restriction.

Protein restriction (PR) during pregnancy induces morphofunctional alterations related to deficient nephrogenesis. We studied the renal functional and morphological significance of PR during pregnancy and/or lactation in adult male rat offspring and the repercussions on acute kidney injury (AKI) severity. Female rats were randomly assigned to the following groups: control diet during pregnancy and lactation (CC), control diet during pregnancy and PR diet during lactation (CR), PR during pregnancy and control diet during lactation (RC), and PR during pregnancy and lactation (RR). Three months after birth, at least 12 male offspring of each group randomly underwent either bilateral renal ischemia for 45 min [ischemia-reperfusion (IR)] or sham surgery. Thus, eight groups were studied 24 h after reperfusion: CC, CC + IR, CR, CR + IR, RC, RC + IR, RR, and RR + IR. Under basal conditions, the CR, RC, and RR groups exhibited a significant reduction in nephron number that was associated with a reduction in renal blood flow. Glomerular hyperfiltration was present as a compensatory mechanism to maintain normal renal function. mRNA levels of several vasoactive, antioxidant, and anti-inflammatory molecules were decreased. After IR, renal function was similarly reduced in all of the studied groups. Although all of the offspring from maternal PR exhibited renal injury, the magnitude was lower in the RC and RR groups, which were associated with faster renal blood flow recovery, differential vasoactive factors, and hypoxia-inducible factor-1α signaling. Our results show that the offspring from maternal PR are resilient to AKI induced by IR that was associated with reduced tubular injury and a differential hemodynamic response.

Maternal Exposure to Bisphenol A Combined with High-Fat Diet-Induced Programmed Hypertension in Adult Male Rat Offspring: Effects of Resveratrol.

Maternal exposure to endocrine disrupting chemicals (EDCs) and a high-fat intake may induce the developmental programming of hypertension in adult offspring. Bisphenol A (BPA) is one of the most commonly environmental EDCs. As the nitric oxide (NO) and aryl hydrocarbon receptor (AHR) signaling pathways both contribute to the pathogenesis of hypertension, we evaluated whether resveratrol, an antioxidant and an AHR antagonist, can prevent hypertension programmed by a maternal BPA and HF diet. Sixteen-week-old male rat offspring were assigned to six groups (n = 8 per group): Control, HF (D12331, Research Diets), BPA (50 μg/kg/day), HF + BPA, BPA + R (resveratrol 50mg/L in drinking water throughout pregnancy and lactation), and HF + BPA + R. Maternal BPA exposure exacerbated hypertension programmed by HF consumption in adult male offspring, which was protected by maternal resveratrol therapy. The BPA and HF diet synergistically induced oxidative stress in offspring kidneys, which resveratrol treatment prevented. We observed that HF + BPA-induced programmed hypertension was associated with a decreased NO bioavailability, increased oxidative stress, and an activated AHR signaling pathway. The beneficial effects of resveratrol are relevant to restoring NO bioavailability, reducing oxidative stress, and antagonizing the AHR signaling pathway. Our results cast a new light on resveratrol as a reprogramming strategy to protect against hypertension programmed by combined BPA and HF exposure, but this strategy has yet to be translated into clinical applications.

Long-term effects of maternal resveratrol intake during lactation on cholesterol metabolism in male rat 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.

Decreased liver triglyceride content in adult rats exposed to protein restriction during gestation and lactation: roles of hepatic lipogenesis and lipid utilization in muscle and adipose tissue.

Protein restriction throughout pregnancy and lactation reduces liver triglyceride (TG) content in adult male rat offspring. The study determined the contribution of hepatic lipogenesis to the reduction in liver TG content. Rats received either control or protein-restricted diets throughout pregnancy and lactation. Offspring were sacrificed on day 65. Hepatic fatty acid uptake and de novo fatty acid and TG biosynthesis were similar between control and low-protein (LP) offspring. These results indicate that hepatic lipogenesis cannot mediate the decrease in liver TG content in LP offspring. We then determined whether increased lipid utilization in adipose tissue and muscle was responsible for the decrease in liver TG content. There was suggestive evidence of increased sympathetic nervous system tone in epididymal adipose tissue of LP offspring that increased fatty acid uptake, TG lipolysis, and utilization of fatty acids in mitochondrial thermogenesis. Measurement of similar parameters demonstrated that such alterations do not occur in gastrocnemius muscle, another major lipid-utilizing tissue. Our results suggest that the decrease in liver TG content in LP offspring is likely due to increased diversion of fatty acids to white and brown adipose tissue depots and their enhanced utilization to fuel mitochondrial thermogenesis.

Influence of prenatal waterpipe tobacco smoke exposure on reproductive hormones and oxidative stress of adult male offspring rats.

Male infertility is adversely affected by tobacco cigarette smoking. Herein, the effects of prenatal waterpipe tobacco smoke (WTS) exposure on reproductive hormones and oxidative stress of adult offspring rats were evaluated. Pregnant rats received either fresh air or mainstream WTS (2hr daily). Pregnancy outcomes, circulatory levels of follicle stimulating hormone (FSH), luteinizing hormone (LH) and prolactin, testicular levels of oestrogen, testosterone and oxidative stress biomarkers [catalase, superoxide dismutase (SOD), glutathione peroxidase (GPx) and thiobarbituric acid reactive substances (TBARS)] were assessed in their adult male offspring rats. Prenatal WTS exposure reduced the number of born offspring, female to pups ratio and birthweight (p<0.05). Prenatal WTS exposure increased the circulatory levels of FSH and the testicular levels of oestrogen, testosterone and TBARS and catalase activity compared with control group (p<0.05). However, GPx activity was reduced by WTS exposure (p<0.05). There appeared to be a trend of increased LH and prolactin levels with prenatal WTS exposure; however, it was not statistically significant compared with control group (p>0.05). The activity of SOD was not affected by prenatal WTS exposure (p>0.05). In conclusion, prenatal WTS exposure altered reproductive hormones as well as oxidative stress biomarkers in adult male offspring rats.

Effects of prenatal exposure to chrysotile asbestos on hippocampal neurogenesis and long-term behavioral changes in adult male rat offspring

Prenatal development is a critical period of life that many environmental pollutants have been suggested to influence fetal growth. Nevertheless, there are still a few investigations into the prenatal exposure to chrysotile asbestos and its neurodevelopmental and behavioral outcome in offspring.In this study, twenty-eight pregnant Wistar rats were divided into four groups and received three-times repeated intraperitoneal injections of normal saline, chrysotile, ascorbic acid and the combination of chrysotile and ascorbic acid on gestational days 11, 14 and 17. The maternal serum levels of malondialdehyde (MDA) and prooxidant-antioxidant balance (PAB) and hippocampal MDA content in adult male offspring were measured. At postnatal day (PND) 60, elevated plus maze was performed to determine anxiety-like behavior, also depression-like behavior was examined using a forced swim test at PND 61- 62. Thereafter, the quantitative analysis of Ki-67, NeuN and GFAP positive cells in the hippocampal dentate gyrus were studied by immunostaining.Our data showed that prenatal exposure to chrysotile increased the maternal serum level of MDA and PAB as well as hippocampal MDA content in adult male offspring, also increased the depression- and anxiety-like behaviors of adult male offspring and decreased the hippocampal Ki-67+, NeuN+ and GFAP+ cells in dantate gyrus of adult male offspring. However, co-administration of ascorbic acid and chrysotile decreased hippocampal lipid peroxidation and increased the Ki-67+, NeuN+ and GFAP+ cells in adult male offspring. In summary, these results indicated that oxidative stress induced by prenatal exposure to chrysotile, lead to the long-lasting decrease of the hippocampal cell proliferation and neuronal differentiation as well as astrogliosis of adult male offspring that exhibit more depression- and anxiety-like behaviors in adulthood and co-treatment of ascorbic acid with chrysotile asbestos attenuated the changes.

Effect of Prenatal Waterpipe Tobacco Smoke Exposure on Cardiac Biomarkers in Adult Offspring Rats.

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. 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. 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). 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.

Effect of waterpipe tobacco smoke exposure during lactation on learning and memory of offspring rats: Role of oxidative stress

AimsThe prevalence of waterpipe tobacco smoking is increasing among breastfeeding women. Herein, the effect of maternal waterpipe tobacco smoke (WTS) exposure during lactation on learning and memory of adult offspring rats was examined. Main methodsLactating rats received either fresh air or mainstream WTS (1 h twice daily) from day 4 to day 21. Learning and memory was examined by the radial arm water maze and the levels of brain derived neurotrophic factor (BDNF) and oxidative stress biomarkers superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase and thiobarbituric acid reactive substances (TBARS) were assessed in the hippocampus of adult male offspring rats. Key findingsMaternal exposure to WTS during lactation impaired the long-term memory and reduced levels of BDNF (P < 0.05) in hippocampus in adult male offspring rats. The activity of SOD, GPx and catalase were reduced (P < 0.05) while level of TBARS was increased (P < 0.05). SignificanceMaternal WTS exposure during lactation impaired the long-term memory of adult male offspring that was associated with low levels of BDNF and altered oxidative stress balance. Therefore, careful measures should be taken to enhance waterpipe smoking cessation during breastfeeding.