Maternal obesity impairs fetal cardiomyocyte contractile function in sheep

Area of Science:

• Cardiovascular Physiology
• Developmental Biology
• Reproductive Health

Background:

• Maternal obesity (MO) is a global health concern, affecting one-third of US women of reproductive age.
• MO in mothers is linked to offspring cardiovascular disease, but the mechanisms are not fully understood.

Purpose of the Study:

• To investigate the impact of maternal obesity on fetal cardiomyocyte contractility in a sheep model.
• To elucidate the underlying cellular and molecular mechanisms responsible for impaired fetal cardiac function.

Main Methods:

• Utilized a sheep model to study fetal cardiomyocyte contractility at term in the context of maternal obesity.
• Assessed cardiomyocyte contractility, intracellular calcium handling, Ca2+-release channel function, and expression/phosphorylation of key contractile proteins.

Main Results:

• Maternal obesity significantly impaired fetal cardiomyocyte contractility, reducing peak shortening and altering relaxation velocity.
• Disrupted intracellular calcium homeostasis was observed, with increased intracellular Ca2+ and impaired Ca2+ release, alongside altered ryanodine receptor-2 phosphorylation.
• Changes in myofilament protein composition, including an increased MHC-β/MHC-α ratio and altered troponin/tropomyosin expression and phosphorylation, were associated with contractile dysfunction.

Conclusions:

• Maternal obesity negatively impacts fetal cardiomyocyte contractility through impaired calcium handling and aberrant myofilament protein composition.
• These findings provide critical insights into the developmental programming of offspring cardiac function and predisposition to cardiovascular disease.
• This study is the first to characterize the effects of maternal obesity on fetal cardiomyocyte contractility, highlighting potential therapeutic targets.