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Growth inhibition and compensation in response to neonatal hypoxia in rats
Shlomit Radom-Aizik1, Frank P Zaldivar, Dwight M Nance
1Department of Pediatrics, Pediatric Exercise Research Center, University of California, Irvine, Irvine, California, USA. saizik@uci.edu
Insights
Hypoxia in infant rats causes inflammation and growth problems, but the heart adapts to survive. This study reveals biomarkers to assess interventions for premature babies.
Area of Science:
- Physiology
- Developmental Biology
- Molecular Biology
Background:
- Hypoxia (Hx) is a key factor in prematurity, asthma, and obesity, leading to chronic inflammation in children.
- Understanding Hx's impact is crucial for addressing health issues in vulnerable populations.
Purpose of the Study:
- To investigate the effects of postnatal hypoxia on growth, inflammation, and gene expression in rat models.
- To identify potential biomarkers for assessing interventions against Hx-induced damage.
Main Methods:
- Postnatal hypoxia (12% O2) exposure in rats from day 2 to 20.
- Comparison with normoxic control and growth-restricted groups.
- Analysis of plasma cytokine levels, growth factors, cardiac and skeletal muscle gene expression (including microRNAs).
Main Results:
- Hx and growth restriction similarly reduced overall growth.
- Hx increased pro-inflammatory cytokines (TNF-α, IL-6) and decreased growth factors (IGF-I, VEGF).
- Hx caused right ventricle hypertrophy and skeletal muscle growth deficits, with altered miR-206 and myostatin expression.
Conclusions:
- Hx triggers a pro-inflammatory state that impairs growth regulation.
- Critical organs like the heart exhibit adaptive mechanisms to survive Hx.
- Identified biomarkers can aid in evaluating therapies for Hx-related conditions in premature infants.
Background:
Hypoxia (Hx) is an important disease mechanism in prematurity, childhood asthma, and obesity. In children, Hx results in chronic inflammation.
Methods:
We investigated the effects of Hx (12% O2) during postnatal days 2-20 in rats. Control groups were normoxic control (Nc), and normoxic growth restricted (Gr) (14-pup litters).
Results:
The Hx-exposed and Gr rats had similar decreases in growth. Hx increased plasma tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6) levels and decreased insulin-like growth factor 1 (IGF-I) and vascular endothelial growth factor (VEGF) levels. Hx resulted in hypertrophy of the right ventricle (RV) but disproportionate decrements in limb skeletal muscle (SM) growth. miR-206 was depressed in the hypertrophied RV of Hx rats but was increased in growth-retarded SM. Hx resulted in decreased RV messenger RNA (mRNA) level for myostatin but had no effect on SM myostatin. The mRNA for Hx-sensitive factors such as hypoxia inducible factor-1α (HIF-1α) was depressed in the RV of Hx rats, suggesting negative feedback.
Conclusion:
The results indicate that Hx induces a proinflammatory state that depresses growth-regulating mechanisms and that tissues critical for survival, such as the heart, can escape from this general regulatory program to sustain life. This study identifies accessible biomarkers for evaluating the impact of interventions designed to mitigate the long-term deleterious consequences of Hx that all too often occur in babies born prematurely.
