Effects of hypoxia-induced intrauterine growth restriction on cardiac siderosis and oxidative stress

We have previously shown that adult rat offspring born intrauterine growth restricted (IUGR) as a result of a prenatal hypoxic insult exhibit several cardiovascular characteristics that are compatible with common manifestations of chronic iron toxicity. As hypoxia is one of the major regulators of iron absorption and metabolism, we hypothesized that hypoxia-induced IUGR offspring will have long-term changes in their ability to regulate iron metabolism leading to myocardial iron deposition and induction of myocardial oxidative stress. Pregnant Sprague Dawley rats were randomized to control (n = 8) or maternal hypoxia (11.5% oxygen; n = 8) during the last 6 days of pregnancy. At birth, litters were reduced to eight pups (four male and four female). At 4 or 12 months of age, offspring were euthanatized and samples (blood and myocardium) were collected. In only the male offspring, IUGR and aging were associated with an increase in myocardial markers of oxidative stress such as oxidized/reduced glutathione ratio and malondialdehyde. Aged male IUGR offspring also exhibited interstitial myocardial remodeling characterized by myocyte loss and disrupted extracellular matrix.Contrary to our hypothesis, however, neither IUGR nor aging were associated with changes in any systemic or local markers of iron metabolism. Our results suggest that hypoxic insults leading to IUGR produce long-term effects on the levels of oxidative stress and connective tissue distribution in the myocardium of male but not female offspring.

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Long-term effects of intrauterine malnutrition on vascular function in female offspring: Implications of oxidative stress

Life Sciences ◽

10.1016/j.lfs.2006.10.028 ◽

2007 ◽

Vol 80 (8) ◽

pp. 709-715 ◽

Cited By ~ 36

Author(s):

Maria C.P. Franco ◽

Eliana H. Akamine ◽

Nancy Rebouças ◽

Maria Helena C. Carvalho ◽

Rita C.A. Tostes ◽

...

Keyword(s):

Oxidative Stress ◽

Vascular Function ◽

Female Offspring ◽

Long Term Effects ◽

Intrauterine Malnutrition

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The long-term bio-behavioural effects of juvenile sildenafil treatment in Sprague-Dawley versus Flinders Sensitive Line rats

Acta Neuropsychiatrica ◽

10.1017/neu.2021.4 ◽

2021 ◽

pp. 1-20

Author(s):

Juandré Lambertus Bernardus Saayman ◽

Stephanus Frederik Steyn ◽

Christiaan Beyers Brink

Keyword(s):

Sprague Dawley ◽

Long Term Effects ◽

Bdnf Level ◽

Treatment Groups ◽

Sd Rats ◽

Behavioural Effects ◽

Sensitive Line ◽

Level Analysis ◽

Flinders Sensitive Line

Abstract Objective: To investigate the long-term effects of juvenile sub-chronic sildenafil (SIL) treatment on the depressive-like behaviour and hippocampal brain-derived neurotrophic factor (BDNF) levels of adult Sprague-Dawley (SD) versus Flinders Sensitive Line (FSL) rats. Methods: SD and FSL rats were divided into pre-pubertal and pubertal groups, whereafter 14-day saline or SIL treatment was initiated. Pre-pubertal and pubertal rats were treated from postnatal day 21 (PND21) and PND35, respectively. The open field and forced swim tests (FST) were performed on PND60, followed by hippocampal BDNF level analysis one day later. Results: FSL rats displayed greater immobility in the FST compared to SD rats (p < 0.0001), which was reduced by SIL (p < 0.0001), regardless of treatment period. Hippocampal BDNF levels were unaltered by SIL in all treatment groups (p > 0.05). Conclusion: Juvenile sub-chronic SIL treatment reduces the risk of depressive-like behaviour manifesting during young adulthood in genetically susceptible rats.

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Second-Generation Consequences of Small-for-Dates Birth

PEDIATRICS ◽

10.1542/peds.84.2.343 ◽

1989 ◽

Vol 84 (2) ◽

pp. 343-347

Author(s):

Mark A. Klebanoff ◽

Olav Meirik ◽

Heinz W. Berendes

Keyword(s):

Confidence Interval ◽

Birth Outcomes ◽

Odds Ratio ◽

Intrauterine Growth Retardation ◽

Long Term Effects ◽

Intrauterine Growth ◽

Increased Risk ◽

Reported Study ◽

Increase In Risk

This is the first reported study of birth outcomes of a group of women whose own birth weights and gestational ages had been previously recorded. Births occurring from 1972 to 1983 among 1154 Swedish women, born from 1955 to 1965, were studied. Women who were themselves small for gestational age (SGA) at birth were at increased risk of giving birth to a SGA infant (odds ratio = 2.21, 95% confidence interval = 1.41, 3.48). Women who had been SGA had an even greater increase in risk of giving birth to a preterm infant (odds ratio = 2.96, 95% confidence interval = 1.47, 5.94). Women who were preterm at birth were not at increased risk of giving birth to either preterm (odds ratio = 0.65, 95% confidence interval = 0.15, 2.74) or SGA (odds ratio 1.21, 95% confidence interval = 0.62, 2.38) infants. It is concluded that the long-term effects of intrauterine growth retardation may extend to the next generation; women who had been SGA should be considered at increased risk to give birth to both growth-retarded and preterm infants.

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Karate Training Improves Metabolic Health in Overweight and Obese Adolescents: A Randomized Clinical Trial

Pediatric Exercise Science ◽

10.1123/pes.2020-0193 ◽

2021 ◽

pp. 1-11

Author(s):

Fabricio de Souza ◽

Luciano Acordi da Silva ◽

Gisele Santinoni Ferreira ◽

Márcia Mendonça Marcos de Souza ◽

Franciane Bobinski ◽

...

Keyword(s):

Oxidative Stress ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Overweight And Obesity ◽

Lipoprotein Cholesterol ◽

Psychological Interventions ◽

Long Term Effects ◽

Low Density Lipoprotein Cholesterol ◽

Stress Markers

Purpose: This study evaluated the effects of 12 weeks of karate training on cardiometabolic parameters, oxidative stress, and inflammation in adolescents with overweight and obesity. Method: Seventy adolescents were randomized into 2 groups: control received nutritional and psychological interventions once a week for 12 weeks, and treatment received nutritional and psychological interventions once a week, plus 3 karate sessions per week, for 12 weeks. The main outcome measure was improvement in cardiometabolic parameters, oxidative stress, and inflammation. Results: After the intervention period, the treatment group showed a reduction in resting heart rate (77.86 [10.89]), high-density lipoprotein cholesterol (40.86 [8.31]), and triglycerides (75.18 [32.29]) and an increase in low-density lipoprotein cholesterol (95.64 [42.53]) in relation to pretraining. Regarding oxidative stress markers, there was a reduction in protein carbonylation (0.07 [0.06]) and nitric oxide (1.39 [1.11]) and an increase in superoxide dismutase (0.68 [0.31]) and glutathione (0.11 [0.08]) compared with pretraining. With respect to inflammation, adiponectin increased (14.54 [5.36]) after the intervention when compared with preintervention. Conclusion: The study concluded that the intervention may improve cardiometabolic parameters, oxidative stress, and inflammation in adolescents with overweight and obesity. Long-term effects need to be evaluated.

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Empirical studies of effects of EDC on reproductive physiology (particularly in females)

Proceedings of the British Society of Animal Science ◽

10.1017/s175275620000613x ◽

2001 ◽

Vol 2001 ◽

pp. 231-231

Author(s):

H M Picton

Keyword(s):

Empirical Studies ◽

Reproductive Function ◽

Endocrine Disrupting Compounds ◽

Female Offspring ◽

Long Term Effects ◽

Endocrine Disrupting ◽

Ovarian Morphology ◽

Wildlife Populations ◽

Male Reproductive Health

Over recent years increasing evidence suggests that xeno-oestrogens including alkylphenols, such as nonylphenol and octlyphenol (OP), may represent a threat to the health and reproductive function of humans, domestic animals and wildlife populations. To date most attention has focused on the effect of these endocrine disrupting compounds (EDCs) on male reproductive health. In contrast, hardly any attention has been paid to the potential adverse effects that these compounds may exert in females, where the end points are easier to measure than in males, and where oestrogen modulated diseases such as breast cancer, are of such importance to humans. This is also despite evidence from a number of species, including humans, that exposure in utero to the potent synthetic oestrogen diethylstilbestrol (DES) has profound and long-term effects on ovarian morphology, folliculogenesis, fertility, and pregnancy outcome of female offspring.

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Antenatal Dexamethasone Exposure Impairs the High-Conductance Ca 2+ -Activated K + Channels via Epigenetic Alteration at Gene Promoter in Male Offspring

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvbaha.120.314905 ◽

2020 ◽

Vol 40 (11) ◽

Author(s):

Ting Xu ◽

Meng Zhao ◽

Huan Li ◽

Xiuwen Zhou ◽

Bailin Liu ◽

...

Keyword(s):

Gene Promoter ◽

Male Offspring ◽

Mesenteric Arteries ◽

Voltage Sensitivity ◽

Sprague Dawley ◽

Long Term Effects ◽

Cardiovascular Risks ◽

Long Term Impact ◽

High Conductance

Objective: Antenatal exposure to glucocorticoids increases cardiovascular risks related to vascular dysfunctions in offspring, although underlying mechanisms are still unknown. As an important vascular mediator, high-conductance Ca 2+ -activated K + channels (BK) plays an essential role in determining vascular tone. Long-term effects of antenatal glucocorticoids on BK in offspring are largely unknown. This study examined the effects and mechanisms of antenatal exposure to clinically relevant doses of glucocorticoids on vascular BK in offspring. Approach and Results: Pregnant Sprague-Dawley rats received synthetic glucocorticoids dexamethasone or vehicle during the last week of pregnancy. Vascular functions, cellular electrophysiology, target gene expression, and promoter methylation were examined in mesenteric arteries of male offspring (gestational day 21 [fetus] and postnatal day 120 [adult offspring]). Antenatal dexamethasone exposure impaired BK activators-mediated relaxation and reduced whole-cell BK currents in mesenteric arteries. Antenatal dexamethasone exposure did not alter Ca 2+ /voltage-sensitivity of BK but downregulated the expressions of BK α and β1 subunits in both fetal and adult mesenteric arteries. In addition, increased promoter methylations within BKα and BKβ1 were compatible with reduced expressions of the 2 genes. Conclusions: Our findings showed a profound and long-term impact of antenatal dexamethasone exposure on vascular BK via an altered epigenetic pattern from fetal stage to adulthood, advancing understanding of prolonged adverse effects and mechanisms of antenatal glucocorticoids exposure on vascular health in offspring.

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Severe but not moderate hyperoxia of newborn mice causes an emphysematous lung phenotype in adulthood without persisting oxidative stress and inflammation

BMC Pulmonary Medicine ◽

10.1186/s12890-019-0993-5 ◽

2019 ◽

Vol 19 (1) ◽

Cited By ~ 2

Author(s):

Anke Kindermann ◽

Leonore Binder ◽

Jan Baier ◽

Beate Gündel ◽

Andreas Simm ◽

...

Keyword(s):

Oxidative Stress ◽

Later Life ◽

Lung Compliance ◽

Elastic Fibers ◽

Newborn Mouse ◽

Long Term Effects ◽

Newborn Mice ◽

Functional Changes ◽

Oxygen Concentrations

Abstract Background Preterm newborns typically require supplemental oxygen but hyperoxic conditions also damage the premature lung. Oxygen-induced lung damages are mainly studied in newborn mouse models using oxygen concentrations above 75% and looking at short-term effects. Therefore, we aimed at the investigation of long-term effects and their dependency on different oxygen concentrations. Methods Newborn mice were exposed to moderate vs. severe hyperoxic air conditions (50 vs. 75% O2) for 14 days followed by a longer period of normoxic conditions. Lung-related parameters were collected at an age of 60 or 120 days. Results Severe hyperoxia caused lower alveolar density, enlargement of parenchymal air spaces and fragmented elastic fibers as well as higher lung compliance with peak airflow limitations and higher sensitivity to ventilation-mediated damages in later life. However, these long-term lung structural and functional changes did not restrict the voluntary physical activity. Also, they were not accompanied by ongoing inflammatory processes, increased formation of reactive oxygen species (ROS) or altered expressions of antioxidant enzymes (superoxide dismutases, catalase) and lung elasticity-relevant proteins (elastin, pro-surfactant proteins) in adulthood. In contrast to severe hyperoxia, moderate hyperoxia was less lung damaging but also not free of long-term effects (higher lung compliance without peak airflow limitations, increased ROS formation). Conclusions Severe but not moderate neonatal hyperoxia causes emphysematous lungs without persisting oxidative stress and inflammation in adulthood. As the existing fragmentation of the elastic fibers seems to play a pivotal role, it indicates the usefulness of elastin-protecting compounds in the reduction of long-term oxygen-related lung damages.

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Long term effects of fetal undernutrition on rat heart. Role of hypertension and oxidative stress

PLoS ONE ◽

10.1371/journal.pone.0171544 ◽

2017 ◽

Vol 12 (2) ◽

pp. e0171544 ◽

Cited By ~ 19

Author(s):

Pilar Rodríguez-Rodríguez ◽

Angel L. López de Pablo ◽

Concha F. García-Prieto ◽

Beatriz Somoza ◽

Begoña Quintana-Villamandos ◽

...

Keyword(s):

Oxidative Stress ◽

Rat Heart ◽

Long Term Effects ◽

And Oxidative Stress

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Prenatal programming of adult blood pressure: role of maternal corticosteroids

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00455.2004 ◽

2005 ◽

Vol 289 (4) ◽

pp. R955-R962 ◽

Cited By ~ 80

Author(s):

Lori L. Woods ◽

Douglas A. Weeks

Keyword(s):

Blood Pressure ◽

Food Intake ◽

Female Offspring ◽

Common Mechanism ◽

Long Term Effects ◽

Pregnant Rats ◽

Body Weights ◽

Glucocorticoid Administration ◽

Blood Pressures

Both maternal glucocorticoid administration and maternal dietary protein or food restriction in pregnancy cause fewer nephrons and hypertension in the adult offspring. The purpose of these studies was to determine the extent to which nutritional factors contribute to programming of offspring hypertension by maternal glucocorticoids. Pregnant rats were treated with dexamethasone (100 μg·kg−1·d−1sc) on days 1–10 (ED) or days 15–20 (LD) of pregnancy. Additional groups of pregnant animals were pair fed to the early (EDPF) and late (LDPF) dexamethasone-treated groups, and another group was untreated or given vehicle (C). The dams treated with dexamethasone reduced their food intake and lost or failed to gain a normal amount of weight during treatment; body weights of ED dams caught up to normal after the treatment period, whereas those of LD dams did not. In adulthood (∼21 wks), chronically instrumented male offspring of ED had normal blood pressures (125 ± 2 mmHg vs. 126 ± 1 mmHg in C), whereas LD offspring were hypertensive (136 ± 3 mmHg). However, LDPF offspring were equally hypertensive (134 ± 2 mmHg). Glomerular filtration rates normalized to body weight were not significantly different among groups. Qualitatively similar results were found in female offspring. Thus the long-term effects of maternal glucocorticoid administration at this dose on offspring’s blood pressure may, in large part, be accounted for by the reduction in maternal food intake. These data suggest that maternal glucocorticoids and maternal food or protein restriction may, at least in part, share a common mechanism in programming offspring for hypertension. The window of sensitivity of future offspring blood pressure to either maternal insult coincides with nephrogenesis in the rat, suggesting that impaired renal development could play an important role in this programming.

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