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Transcriptome and morphological analysis on the heart in gestational protein-restricted aging male rat offspring
Marina S Folguieri1, Ana Teresa Barufi Franco1, André Schwambach Vieira2
1Fetal Programming and Hydroelectrolyte Metabolism Laboratory, Nucleus of Medicine and Experimental Surgery, Department of Internal Medicine, FCM, Campinas, Brazil.
Insights
Maternal protein restriction during pregnancy in rats leads to low birth weight and later-life heart problems, including high blood pressure and fibrosis. This suggests a link between diet, gene expression, and progressive heart failure in offspring.
Area of Science:
- Developmental programming of cardiovascular disease
- Epigenetics and fetal development
- Nutritional influences on long-term health
Background:
- Adverse developmental factors increase risks for adult cardiovascular disease (CVD), diabetes, and hypertension.
- Intrauterine conditions, like protein restriction, may program long-term cardiovascular abnormalities.
- Gestational protein restriction can cause heart changes, potentially linked to epigenetic effects and reduced lifespan.
Purpose of the Study:
- To investigate the long-term cardiac consequences of gestational protein restriction in Wistar rats.
- To determine if maternal low-protein diet impacts offspring's cardiovascular health and gene expression.
- To explore the relationship between early-life nutrition and adult heart dysfunction.
Main Methods:
- Wistar rats were fed either a normal protein (NP, 17%) or low-protein (LP, 6%) diet during pregnancy.
- Offspring cardiovascular parameters were assessed at 62 weeks, including blood pressure, cardiac mass, cardiomyocyte size, and collagen content.
- Gene expression analysis (mRNA sequencing) was performed on cardiac tissue to identify molecular changes.
Main Results:
- Low-protein diet offspring exhibited low birth weight, catch-up growth, hypertension, increased heart collagen, and larger cardiomyocyte area.
- mRNA sequencing revealed significant alterations in 137 genes related to inflammation, oxidative stress, apoptosis, autophagy, hypertrophy, and fibrosis.
- Despite no significant adj-p-value changes, pathway analysis indicated substantial molecular shifts contributing to heart dysfunction.
Conclusions:
- Gestational protein restriction induces early-onset cardiac disease in rat offspring.
- Heart dysfunction is associated with fibrosis, myocyte hypertrophy, and abnormal gene expression patterns.
- A strong link exists between maternal protein restriction, specific gene expression profiles, and progressive heart failure.
Abstract:
Background: Adverse factors that influence embryo/fetal development are correlated with increased risk of cardiovascular disease (CVD), type-2 diabetes, arterial hypertension, obesity, insulin resistance, impaired kidney development, psychiatric disorders, and enhanced susceptibility to oxidative stress and inflammatory processes in adulthood. Human and experimental studies have demonstrated a reciprocal relationship between birthweight and cardiovascular diseases, implying intrauterine adverse events in the onset of these abnormalities. In this way, it is plausible that confirmed functional and morphological heart changes caused by gestational protein restriction could be related to epigenetic effects anticipating cardiovascular disorders and reducing the survival time of these animals. Methods: Wistar rats were divided into two groups according to the protein diet content offered during the pregnancy: a normal protein diet (NP, 17%) or a Low-protein diet (LP, 6%). The arterial pressure was measured, and the cardiac mass, cardiomyocytes area, gene expression, collagen content, and immunostaining of proteins were performed in the cardiac tissue of male 62-weeks old NP compared to LP offspring. Results: In the current study, we showed a low birthweight followed by catch-up growth phenomena associated with high blood pressure development, increased heart collagen content, and cardiomyocyte area in 62-week-old LP offspring. mRNA sequencing analysis identified changes in the expression level of 137 genes, considering genes with a p-value < 0.05. No gene was. Significantly changed according to the adj-p-value. After gene-to-gene biological evaluation and relevance, the study demonstrated significant differences in genes linked to inflammatory activity, oxidative stress, apoptosis process, autophagy, hypertrophy, and fibrosis pathways resulting in heart function disorders. Conclusion: The present study suggests that gestational protein restriction leads to early cardiac diseases in the LP progeny. It is hypothesized that heart dysfunction is associated with fibrosis, myocyte hypertrophy, and multiple abnormal gene expression. Considering the above findings, it may suppose a close link between maternal protein restriction, specific gene expression, and progressive heart failure.
