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Long-term multi-organ system abnormalities in mice exposed to antenatal and postnatal corticosteroids

Abstract

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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Fig. 1: Body weight is decreased in adult mice exposed to ANCS + PNCS.
Fig. 2: Alveolarization is decreased in mice exposed to ANCS + PNCS.
Fig. 3: Cardiomyocyte diameter is increased in mice exposed to ANCS + PNCS.
Fig. 4: Liver metabolic markers are decreased in mice exposed to ANCS + PNCS.
Fig. 5: Liver FFA are decreased in mice exposed to ACS + PCS.

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Data availability

Data are available by written request to jdillard@akronchildrens.org.

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Funding

This study was funded by grants from the Saint Louis University School of Medicine President’s Research Fund and Cardinal Glennon Children’s Foundation. The funders played no role in the design, analysis, and reporting of the study.

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Conception and design: Julie Dillard, Noah Hillman; Acquisition of data: Julie Dillard, Emily Royse; Analysis and interpretation of data: Julie Dillard, Emily Royse, Noah Hillman; Manuscript preparation: Julie Dillard, Emily Royse, Noah Hillman; All authors approved the final manuscript as submitted.

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Correspondence to Julie A. Dillard.

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Dillard, J.A., Royse, E.X. & Hillman, N.H. Long-term multi-organ system abnormalities in mice exposed to antenatal and postnatal corticosteroids. Pediatr Res (2025). https://doi.org/10.1038/s41390-025-04373-7

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