Brief, Intermittent Hypoxia Restricts Fetal Growth in Sprague-Dawley Rats

Schwartz, Jonathan E.; Kovách, A. G.; Meyer, Joseph P.; McConnell, Carol; Iwamoto, Harriet S.

doi:10.1159/000013990

Cited by 44 publications

(40 citation statements)

References 24 publications

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“…This characteristic growth trajectory can be altered in rate and timing by exogenous modifiers. Two important non-genetic, environmental effects on the growth pattern are undernutrition (1)(2)(3)(4)(5)(6)(7)(8) and hypoxia (defined in terms of hypoxaemia, anaemia or increased Hb-oxygen affinity at sea level) (9)(10)(11)(12)(13) .On the basis of clinical paediatric findings (13)(14)(15) , we have developed a nutritional stress model in rats (nutritional growthretarded rats): weanling male rats placed on a 20 % restricted balanced diet for a 28-d period closely resembled the suboptimal nutrition observed in children who consume inappropriate diets with insufficient total energy to sustain normal growth and weight gain (16) . Rats maintained on this type of chronic suboptimal nutrition decreased their body mass growth rate, which was one of several described manifestations of nutritional inadequacy.…”

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“…On the basis of clinical paediatric findings (13)(14)(15) , we have developed a nutritional stress model in rats (nutritional growthretarded rats): weanling male rats placed on a 20 % restricted balanced diet for a 28-d period closely resembled the suboptimal nutrition observed in children who consume inappropriate diets with insufficient total energy to sustain normal growth and weight gain (16) . Rats maintained on this type of chronic suboptimal nutrition decreased their body mass growth rate, which was one of several described manifestations of nutritional inadequacy.…”

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Effect of chronic undernutrition on body mass and mechanical bone quality under normoxic and altitude hypoxic conditions

et al. 2016

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Both undernutrition and hypoxia exert a negative influence on both growth pattern and bone mechanical properties in developing rats. The present study explored the effects of chronic food restriction on both variables in growing rats exposed to simulated high-altitude hypoxia. Male rats (n 80) aged 28 d were divided into normoxic (Nx) and hypoxic (Hx) groups. Hx rats were exposed to hypobaric air (380 mmHg) in decompression chambers. At T 0 , Nx and Hx rats were subdivided into four equal subgroups: normoxic control and hypoxic controls, and normoxic growth-restricted and hypoxic growth-restricted received 80 % of the amount of food consumed freely by their respective controls for a 4-week period. Half of these animals were studied at the end of this period (T 4 ). The remaining rats in each group continued under the same environmental conditions, but food was offered ad libitum to explore the type of catch-up growth during 8 weeks. Structural bone properties (strength and stiffness) were evaluated in the right femur midshaft by the mechanical three-point bending test; geometric properties (length, cross-sectional area, cortical mass, bending cross-sectional moment of inertia) and intrinsic properties of the bone tissue (elastic modulus) were measured or derived from appropriate equations. Bone mineralisation was assessed by ash measurement of the left femur. These data indicate that the growth-retarded effects of diminished food intake, induced either by food restriction or hypoxia-related inhibition of appetite, generated the formation of corresponding smaller bones in which subnormal structural and geometric properties were observed. However, they seemed to be appropriate to the body mass of the animals and suggest, therefore, that the bones were not osteopenic. When food restriction was imposed in Hx rats, the combined effects of both variables were additive, inducing a further reduction of bone mass and bone load-carrying capacity. In all cases, the mechanical properties of the mineralised tissue were unaffected. This and the capacity of the treated bones to undergone complete catch-up growth with full restoration of the biomechanical properties suggest that undernutrition, under either Nx or Hx conditions, does not affect bone behaviour because it remains appropriate to its mechanical functions.Key words: Undernutrition: Hypoxia: Bone quality: Biomechanics: Catch-up growth: Body massThe growing rat appears to follow an individual size-age trajectory to its body mass end point. This characteristic growth trajectory can be altered in rate and timing by exogenous modifiers. Two important non-genetic, environmental effects on the growth pattern are undernutrition (1)(2)(3)(4)(5)(6)(7)(8) and hypoxia (defined in terms of hypoxaemia, anaemia or increased Hb-oxygen affinity at sea level) (9)(10)(11)(12)(13) .On the basis of clinical paediatric findings (13)(14)(15) , we have developed a nutritional stress model in rats (nutritional growthretarded rats): weanling male rats placed on a 20 % restricted balan...

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Effect of chronic undernutrition on body mass and mechanical bone quality under normoxic and altitude hypoxic conditions

et al. 2016

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“…One study, using intermittent hypoxic episodes in dams from E15-E19 (FiO 2 5 0.09-0.095) for 1 hr resulted in decreased fetal body weight, and 2 hr resulted in decreased maternal food intake and weight gain (Schwartz et al, 1998). Gozal et al (2003) used a paradigm that utilized IH (10% O 2 ) every 90 sec during the gestational period, and found long lasting changes in the control of breathing, but no changes in spatial task acquisition and retention.…”

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Neuronal migration is transiently delayed by prenatal exposure to intermittent hypoxia

et al. 2005

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BACKGROUND: Neonatal neurodevelopment is influenced by a variety of external factors, although the mechanisms responsible are poorly understood. Prenatal hypoxia, from physiological or chemical sources, can have no discernible effect, or can result in a broad spectrum of abnormalities. METHODS: To mimic some of the maternal effects of smoking, we developed a model that investigates the effects of intermittent hypoxia (IH), with or without concurrent nicotine in timed pregnant Sprague-Dawley rats. RESULTS: We found no significant differences between litter sizes or birthweight of pups from any treatment group, but animals exposed to IH (with or without nicotine) showed long term diminished body weights. Animals subjected to IH consistently showed a transient delay in neuronal migration early in the postpartum period, which was amplified by concurrent nicotine administration. We observed increased c-Abl protein levels in animals from the IH treatment groups. Multiple proteins involved in the intricate control of neuronal migration were also altered in response to this treatment, primarily the downstream targets of c-Abl: Cdk5, p25, and the cytoskeletal elements neurofilament H and F-actin and catalase. Catalase activity and protein levels, already elevated in response to IH, were further amplified by simultaneous nicotine exposure. CONCLUSIONS: This new model provides a novel system for investigating the effects of low grade IH in the developing brain and suggests that concurrent nicotine further aggravates many of the deleterious effects of IH. We also describe IH as a previously unreported mechanism for c-Abl expression. Birth Defects Res B 74:287-299, 2005. r 2005 Wiley-Liss, Inc.

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“…Throughout the literature, there are no concise investigations of scorpion toxin pharmacology during conception. Because of that, we speculate the indirect embryotoxic effects of this envenoming which could originate from the excessive release of reactive oxygen species, especially in fetal tissues, and the maternal hemodynamic alteration that are implicated in embryo-fetal development and growth perturbations (1,6,(30)(31)(32)(33).…”

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Embryotoxicity following repetitive maternal exposure to scorpion venom

Hmed¹,

Badraoui²,

Serria³

et al. 2012

J. Venom. Anim. Toxins incl. Trop. Dis

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Abstract:Although it is a frequent accident in a few countries, scorpion envenomation during pregnancy remains scarcely studied. In the present study, the effects of repetitive maternal exposure to Buthus occitanus tunetanus venom are investigated and its possible embryotoxic consequences on rats. Primigravid rats received a daily intraperitoneal dose of 1 mL/kg of saline solution or 300 µg/kg of crude scorpion venom, from the 7 th to the 13 th day of gestation. On the 21 st day, the animals were deeply anesthetized using diethylether. Then, blood was collected for chemical parameter analysis. Following euthanasia, morphometric measurements were carried out. The results showed a significant increase in maternal heart and lung absolute weights following venom treatment. However, the mean placental weight per rat was significantly diminished. Furthermore, blood urea concentration was higher in exposed rats (6.97 ± 0.62 mmol/L) than in those receiving saline solution (4.94 ± 0.90 mmol/L). Many organs of venom-treated rat fetuses (brain, liver, kidney and spleen) were smaller than those of controls. On the contrary, fetal lungs were significantly heavier in fetuses exposed to venom (3.2 ± 0.4 g) than in the others (3.0 ± 0.2 g). Subcutaneous blood clots, microphthalmia and total body and tail shortening were also observed in venom-treated fetuses. It is concluded that scorpion envenomation during pregnancy potentially causes intrauterine fetal alterations and growth impairment.

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Brief, Intermittent Hypoxia Restricts Fetal Growth in Sprague-Dawley Rats

Cited by 44 publications

References 24 publications

Effect of chronic undernutrition on body mass and mechanical bone quality under normoxic and altitude hypoxic conditions

Effect of chronic undernutrition on body mass and mechanical bone quality under normoxic and altitude hypoxic conditions

Neuronal migration is transiently delayed by prenatal exposure to intermittent hypoxia

Embryotoxicity following repetitive maternal exposure to scorpion venom

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