Prenatal glucocorticoid exposure programs long-term left ventricular metabolism, function, and remodeling in baboons.

Area of Science:

• Cardiovascular Science
• Developmental Biology
• Metabolic Research

Background:

• Synthetic glucocorticoids (sGC) are administered to pregnant women to prevent premature birth complications.
• Emerging evidence suggests prenatal sGC exposure may be linked to adverse cardiovascular outcomes in offspring.
• The long-term cardiovascular and metabolic consequences of fetal sGC exposure require further investigation.

Purpose of the Study:

• To investigate the long-term effects of in utero synthetic glucocorticoid (sGC) exposure on cardiovascular structure, function, and metabolism in adult baboons.
• To compare outcomes between offspring exposed to sGC and saline-exposed controls, examining age and sex-specific differences.

Main Methods:

• Adult baboons exposed to sGC or saline in utero were studied.
• Magnetic resonance imaging assessed heart structure, function, and paracardial adipose thickness (PAT) in middle-aged and old baboons.
• Postmortem left ventricular tissues were analyzed for mitochondrial function and protein expression.

Main Results:

• sGC-exposed males showed age-related increases in left ventricular (LV) sphericity indexes and decreased global longitudinal strain (GLS).
• Increased PAT and altered LV function (ejection fraction, sphericity) were observed in elderly sGC-exposed baboons, with sex-specific differences.
• Reduced mitochondrial Complex I respiration was found in sGC-exposed baboons, with a negative correlation between PAT and mitochondrial protein in males.

Conclusions:

• In utero sGC exposure impairs cardiac structure, function, and metabolism in a sex-specific manner in adult baboons.
• These findings highlight potential long-term cardiovascular risks associated with antenatal sGC exposure.
• Enhanced lifelong monitoring is recommended to understand sex-specific mechanisms and inform clinical practice regarding antenatal sGC use.