Prenatal Bisphenol A Exposure Impairs Fetal Heart Development: Molecular and Structural Alterations with Sex-Specific...

Area of Science:

• Endocrinology
• Developmental Biology
• Cardiovascular Science

Background:

• Cardiovascular diseases (CVDs) are a leading global health concern, with prenatal origins increasingly recognized.
• Endocrine-disrupting chemicals (EDCs) like bisphenol A (BPA) may interfere with fetal programming, predisposing individuals to long-term cardiovascular vulnerability.
• The sex-specific effects of prenatal EDC exposure on fetal heart development are not fully understood.

Purpose of the Study:

• To investigate the molecular and structural impacts of low-dose prenatal BPA exposure on fetal rat hearts.
• To elucidate the sex-dependent mechanisms underlying BPA-induced cardiovascular alterations.
• To explore the role of ER signaling, inflammation, oxidative stress, and fibrosis in BPA-mediated cardiac disruption.

Main Methods:

• Low-dose BPA exposure in pregnant rats during critical fetal development periods.
• Analysis of estrogen receptor (ERα, ERβ, GPER) expression.
• Assessment of inflammatory markers (NF-κB, IL-1β, TNF-α, NLRP3), oxidative stress indicators (SOD1, SOD2, CAT, SELENOT, GPX4, MDA, ACSL4), and ferroptosis.
• Quantification of cardiac distension markers (ANP, BNP), extracellular matrix remodeling, and pro-fibrotic regulators (Col1A1, Col3A1, TGF-β, CTGF).
• Histological examination of cardiac structure, fiber architecture, vascular remodeling (CD34, Ki67), and glycogen content.
• Sex-specific comparative analysis of molecular and structural changes.

Main Results:

• BPA exposure induced sex-dependent disruption of estrogen receptor signaling.
• Significant increases in inflammation, oxidative stress, and ferroptosis were observed, with greater impact in males.
• Markers of cardiac distension, fibrosis, and extracellular matrix remodeling were elevated, particularly in male fetal hearts.
• Histological analysis revealed structural abnormalities, altered myocardial architecture, and vascular remodeling in a sex-specific manner.
• Glycogen depletion and metabolic stress indicators were more pronounced in male fetal hearts.

Conclusions:

• Prenatal BPA exposure disrupts fetal heart development through sex-specific mechanisms involving ER signaling, inflammation, oxidative stress, and fibrosis.
• These disruptions contribute to the early origins of CVD, with males exhibiting greater vulnerability.
• Findings highlight the critical role of prenatal endocrine disruption in long-term cardiovascular health and underscore the need for preventive strategies.