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Antenatal Glucocorticoid Exposure Induced Neurodegenerative Changes in the Fetal Ovine Hippocampal Transcriptome Independent of Pulmonary Immaturity

ABSTRACT: [Background] Antenatal steroid (ACS) therapy conveys lifesaving benefits to the preterm fetus. However, current treatments are associated with increased risk of growth, endocrine, and neurodevelopmental abnormalities. [Objectives] To inform ACS therapy optimisation we used a sheep model of pregnancy to test whether adverse fetal brain effects were independent of respiratory benefit and ACS pharmacokinetics. [Study Design] Ewes carrying a single fetus received intramuscular injections of either: i) 2 x 12mg dexamethasone phosphate 12 hourly (DexP) (Dex High); ii) 4 x 1.5mg DexP 12 hourly (Dex Low); iii) 1 x 0.125mg/kg betamethasone acetate (Beta-Acetate); or iv) Saline (Negative Control). Lambs were delivered for ventilation after 48 hours. Hippocampal and lung tissues were subjected to RNA sequencing. [Results] Dex High treatment did not mature the preterm ovine lung. Pulsatile (Dex High and Dex Low) treatments caused hippocampal RNA changes consistent with neuronal death. Constant, low-amplitude treatment (Beta Acetate) significantly improved lung function, with few adverse RNA transcriptional changes in the fetal hippocampus. [Conclusions] All ACS exposures caused significant alterations in fetal homeostasis. Pulsatile exposures caused dose-independent neurodegenerative changes in the fetal hippocampus. These data highlight the importance of considering magnitude, duration and stability of fetal glucocorticoid exposures in optimising ACS therapy.

ORGANISM(S): Ovis aries

PROVIDER: GSE248786 | GEO | 2024/09/13

REPOSITORIES: GEO

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Antenatal Glucocorticoid Exposure Induced Neurodegenerative Changes in the Fetal Ovine Hippocampal Transcriptome Independent of Pulmonary Immaturity

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