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Published on: December 28, 2011
Sex differences in cardiac transcriptomic response to neonatal sleep apnea
Emily C Cheung1,2, Anna Nilsson3, Ian Venter3
1Department of Biomedical Engineering, The George Washington University, Washington, District of Columbia, USA.
Insights
Pediatric obstructive sleep apnea impacts male and female neonates differently. Males show more significant gene expression changes and potential cardiac issues, highlighting sex-specific risks.
Area of Science:
- Cardiovascular Physiology
- Neonatal Health
- Sleep Medicine
Background:
- Pediatric obstructive sleep apnea (OSA) carries significant cardiovascular risks.
- Understanding sex-specific effects of early-life OSA is crucial for long-term health outcomes.
Purpose of the Study:
- To investigate the sex-specific cardiac responses of neonates to chronic intermittent hypoxia (CIH).
- To identify differences in physiological and molecular pathways between male and female neonates exposed to CIH.
Main Methods:
- Neonates were exposed to CIH until postnatal day 28.
- In vivo physiological assessments included plethysmography, stress tests, and echocardiography.
- Transcriptomic analysis of left ventricular tissue was performed.
Main Results:
- Male CIH rats had reduced body weight and thinner left ventricular walls compared to controls.
- Female neonates showed increased respiratory drive during sleep.
- Males exhibited more pronounced gene expression alterations, with dysregulated miRNAs targeting metabolic genes and genes involved in cardiac action potential.
Conclusions:
- Neonatal exposure to CIH induces distinct cardiovascular and molecular responses in males and females.
- Males appear more susceptible to CIH-related cardiac metabolic alterations and potential arrhythmias.
- These findings underscore the importance of sex-specific approaches in managing pediatric sleep apnea and its cardiovascular consequences.
Abstract:
Pediatric obstructive sleep apnea poses a significant health risk, with potential long-term consequences on cardiovascular health. This study explores the dichotomous nature of neonatal cardiac response to chronic intermittent hypoxia (CIH) between males and females, aiming to fill a critical knowledge gap in the understanding of sex-specific cardiovascular consequences of sleep apnea in early life. Neonates were exposed to CIH until p28 and underwent comprehensive in vivo physiological assessments, including whole-body plethysmography, treadmill stress-tests, and echocardiography. Results indicated that male CIH rats weighed 13.7% less than age-matched control males (p = 0.0365), while females exhibited a mild yet significant increased respiratory drive during sleep (93.94 ± 0.84 vs. 95.31 ± 0.81;p = 0.02). Transcriptomic analysis of left ventricular tissue revealed a substantial sex-based difference in the cardiac response to CIH, with males demonstrating a more pronounced alteration in gene expression compared to females (5986 vs. 3174 genes). The dysregulated miRNAs in males target metabolic genes, potentially predisposing the heart to altered metabolism and substrate utilization. Furthermore, CIH in males was associated with thinner left ventricular walls and dysregulation of genes involved in the cardiac action potential, possibly predisposing males to CIH-related arrhythmia. These findings emphasize the importance of considering sex-specific responses in understanding the cardiovascular implications of pediatric sleep apnea.
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