Long-Term Transcriptomic Changes and Cardiomyocyte Hyperpolyploidy after Lactose Intolerance in Neonatal Rats

Area of Science:

• Cardiovascular Science
• Developmental Biology
• Molecular Biology

Background:

• Cardiovascular diseases can stem from early life growth issues.
• The precise mechanisms linking neonatal development to adult heart health are not fully understood.

Purpose of the Study:

• To investigate if systemic inflammation from neonatal lactose intolerance (NLI) impacts cardiac development and cardiomyocyte gene regulation long-term.
• To test the hypothesis that NLI triggers lasting pathological changes in heart development.

Main Methods:

• Utilized a rat model of NLI induced by lactose overload.
• Employed cytophotometry, image analysis, and mRNA sequencing (mRNA-seq).
• Evaluated cardiomyocyte ploidy, DNA damage, and transcriptomic alterations.

Main Results:

• NLI led to sustained growth retardation and cardiomyocyte hyperpolyploidy in rats.
• Observed significant transcriptomic changes associated with heart pathologies like inflammation, fibrosis, and DNA instability.
• Identified impaired thyroid hormone, calcium, and glutathione signaling as potential causes.
• Found gene expression patterns linked to increased cardiomyocyte polyploidy and open chromatin.

Conclusions:

• Neonatal inflammation due to NLI can permanently alter cardiac gene regulatory networks and cardiomyocyte transcriptome.
• These ploidy-related epigenetic changes acquired neonatally may predispose to adult cardiovascular disease.
• NLI is a potential trigger for developmental programming of adult heart conditions, suggesting avenues for preventive strategies.