Long-term multi-organ system abnormalities in mice exposed to antenatal and postnatal corticosteroids
Julie A Dillard1, Emily X Royse2, Noah H Hillman2
1Division of Neonatology, Akron Children's Hospital, Akron, OH, USA. jdillard@akronchildrens.org.
Insights
Exposure to antenatal and postnatal corticosteroids in mice leads to long-term lung simplification, heart changes, and altered liver metabolism, impacting cardiometabolic health.
Area of Science:
- Perinatal medicine
- Developmental biology
- Cardiometabolic health
Background:
- Exogenous corticosteroid exposure is frequent in premature infants.
- Potential long-term effects on cardiometabolic health are unknown.
Purpose of the Study:
- To investigate long-term cardiometabolic health outcomes in mice exposed to antenatal corticosteroid (ANCS) and postnatal corticosteroid (PNCS).
Main Methods:
- Pregnant mice received dexamethasone (ANCS). Offspring received dexamethasone or saline (PNCS) for the first three days of life.
- Offspring were assessed at 90 days for lung, heart, and liver changes.
Main Results:
- ANCS + PNCS exposure resulted in decreased body weight and lung alveolar simplification.
- Increased cardiomyocyte diameter and altered liver mRNA levels related to energy homeostasis were observed.
- Changes in free fatty acids were also noted in the ANCS + PNCS group.
Conclusions:
- Combined antenatal and short postnatal corticosteroid exposure induces lasting multi-organ system changes in adult mice.
- This includes impaired lung development, cardiac hypertrophy, and metabolic alterations.
- Findings suggest potential long-term morbidities in premature infants exposed to corticosteroids.
Background:
Exogenous corticosteroid exposure is common in premature infants and can interfere with normal developmental processes. It remains unknown if there are long-term alterations to cardiometabolic health following antenatal corticosteroid (ANCS) plus postnatal corticosteroid (PNCS) exposure.
Methods:
Pregnant mice received intraperitoneal (IP) injections of dexamethasone 0.5 mg/kg on gestational days 15-16. Pups delivered naturally. On postnatal days (PD) 1-3, offspring received IP injections of dexamethasone 1.2 mg/kg or saline control. On PD 90, offspring were euthanized and organs harvested for study.
Results:
Compared to ANCS alone, offspring exposed to ANCS + PNCS had decreased body weights, and lungs had alveolar simplification with increased mean linear intercept and decreased radial alveolar count. Exposure to ANCS + PNCS increased cardiomyocyte diameter compared to ANCS alone. Mice exposed to ANCS + PNCS had attenuation in liver mRNA levels in genes responsible for energy homeostasis including adiponectin, peroxisome proliferator-activated receptor gamma coactivator 1-alpha, and sirtuin 1, and alterations in free fatty acids.
Conclusions:
Young adult mice exposed to ANCS + PNCS compared to ANCS alone have evidence of lung simplification, cardiomyocyte hypertrophy, and metabolism-related gene alterations in liver. This study is limited by the lack of a control group with no exposure to corticosteroids.
Impact:
Antenatal + short course of postnatal corticosteroid exposure (3 days) results in long-term multi-organ system changes in adult mice. Mice exposed to antenatal + postnatal corticosteroids exhibit impaired alveolarization, cardiomyocyte hypertrophy, and metabolic alterations in young adulthood. Corticosteroids are a common exposure in premature infants and may contribute to long-term morbidities in this population.
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