Maternal bisphenol a exposure impacts the fetal heart transcriptome

Area of Science:

• Environmental Toxicology
• Developmental Biology
• Cardiovascular Science

Background:

• Fetal development is sensitive to environmental exposures, particularly endocrine disruptors like bisphenol A (BPA).
• Maternal BPA exposure crosses the placenta, necessitating investigation into its effects on fetal organogenesis, specifically cardiac development.
• Previous studies indicate BPA affects multiple organ systems, but its impact on the fetal heart remains largely unexamined.

Purpose of the Study:

• To investigate the effects of gestational bisphenol A (BPA) exposure on the fetal heart transcriptome in non-human primates.
• To assess alterations in gene expression related to cardiac function and pathology following maternal BPA administration.

Main Methods:

• Pregnant rhesus monkeys received daily oral doses of BPA (400 µg/kg) during early or late gestation.
• Fetal heart tissues were collected, and chamber-specific transcriptomes were analyzed using genome-wide microarrays.
• Quantitative real-time PCR and glycogen content analysis were performed on select genes and tissues.

Main Results:

• BPA exposure significantly altered the transcription of genes involved in cardiac pathophysiology.
• Down-regulation of myosin heavy chain, cardiac isoform alpha (Myh6) was observed in the left ventricle.
• Up-regulation of 'A Disintegrin and Metalloprotease 12', long isoform (Adam12-l) occurred in both ventricles and the right atrium.

Conclusions:

• Gestational BPA exposure impacts fetal heart gene expression in rhesus monkeys, suggesting potential adverse effects on cardiovascular development.
• Alterations in key genes like Myh6 and Adam12-l support the hypothesis that BPA exposure may compromise cardiovascular fitness.
• These findings raise concerns about the role of BPA in the development of human metabolic and cardiovascular diseases.