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Fetal Mouse Cardiovascular Imaging Using a High-frequency Ultrasound 30/45MHZ System
Published on: May 5, 2018
Circadian disruption during fetal development promotes pathological cardiac remodeling in male mice
Yang Yu1,2, Jing-Yu Liu1, Hui-Jiao Yang1
1Key Laboratory of Medical Electrophysiology, Ministry of Education & Medical Electrophysiological Key Laboratory of Sichuan Province, (Collaborative Innovation Center for Prevention of Cardiovascular Diseases), Institute of Cardiovascular Research, Southwest Medical University, Luzhou, Sichuan 646000, China.
Insights
Fetal exposure to chronic circadian disturbance (CCD) increases male mice susceptibility to heart disease. This disruption leads to cardiac remodeling and heart failure biomarkers, linked to SCGB1A1 gene upregulation.
Area of Science:
- Cardiovascular Biology
- Developmental Biology
- Chronobiology
Background:
- Circadian rhythm disruption during fetal development is a potential risk factor for adult heart disease.
- Sex-specific effects of intrauterine environmental exposures on cardiovascular health are not fully understood.
Purpose of the Study:
- To investigate the long-term effects of chronic circadian disturbance (CCD) during fetal development on cardiac health in male and female mice.
- To identify molecular mechanisms underlying sex-dependent cardiac remodeling following in utero CCD exposure.
Main Methods:
- Mice were exposed to chronic circadian disturbance (CCD) or normal conditions in utero.
- Postnatal cardiac structure, function, and gene expression were assessed in adult male and female offspring.
- Cardiac function was evaluated using echocardiography and electrophysiology.
- The role of the secretoglobin gene (Scgb1a1) was investigated through overexpression studies.
Main Results:
- Male mice exposed to in utero CCD exhibited significant pathological cardiac remodeling, including ventricular dilatation, fibrosis, and reduced contractility.
- CCD-exposed males showed increased susceptibility to tachyarrhythmia and elevated heart failure biomarkers.
- Gene expression analysis revealed sex-dependent changes, with significant upregulation of Scgb1a1 in the hearts of males exposed to CCD.
- Cardiac overexpression of Scgb1a1 in male mice was sufficient to induce myocardial hypertrophy.
Conclusions:
- In utero exposure to chronic circadian disturbance predisposes male mice to pathological cardiac remodeling and heart failure later in life.
- Upregulation of the Scgb1a1 gene in males appears to be a key mechanism mediating this cardiac susceptibility.
- These findings highlight the critical impact of early-life circadian environment on long-term cardiovascular health in a sex-dependent manner.
Abstract:
Disruption of circadian rhythms during fetal development may predispose mice to developing heart disease later in life. Here, we report that male, but not female, mice that had experienced chronic circadian disturbance (CCD) in utero were more susceptible to pathological cardiac remodeling compared with mice that had developed under normal intrauterine conditions. CCD-treated males showed ventricular chamber dilatation, enhanced myocardial fibrosis, decreased contractility, higher rates of induced tachyarrhythmia, and elevated expression of biomarkers for heart failure and myocardial remodeling. In utero CCD exposure also triggered sex-dependent changes in cardiac gene expression, including upregulation of the secretoglobin gene, Scgb1a1, in males. Importantly, cardiac overexpression of Scgb1a1 was sufficient to induce myocardial hypertrophy in otherwise naive male mice. Our findings reveal that in utero CCD exposure predisposes male mice to pathological remodeling of the heart later in life, likely as a consequence of SCGB1A1 upregulation.
