Analysis of bisphenol A-modulated expression of hypothalamic thyroid, estrogen, and peroxisome proliferator-activated receptors and concurrent mitochondrial dynamics following short-term exposure in mice

Endocrine-disrupting chemicals (EDCs) represent a significant and growing threat to human and animal health, exerting tissue- and concentration-specific effects on endocrine function. This study investigated the acute impact of bisphenol A (BPA) on nuclear receptor signaling and mitochondrial dynamics in hypothalamic AgRP-NPY (agouti-related peptide; neuropeptide Y) and POMC (pro-opiomelanocortin) neurons. Mice received a single intraperitoneal injection of BPA at doses of 40 µg/kg, 5 mg/kg, or 10 mg/kg, and were assessed 6 h post-exposure. Quantitative analysis of hypothalamic mRNA expression revealed that low-dose BPA (40 µg/kg) didn't affect ERα (estrogen receptor alpha), TRα (thyroid receptor alpha), but significantly upregulated PPARγ (peroxisome proliferator-activated receptor gamma). Concurrently, mitochondrial respiration and ultrastructure exhibited dose-dependent alterations, with diminished effects observed at higher BPA concentrations. These findings demonstrate that BPA elicits rapid, dose-dependent modulation of nuclear receptor gene expression and mitochondrial dynamics in hypothalamic neurons. The data suggest mitochondria serve as early subcellular targets of EDC exposure. This underscores the importance of evaluating low-dose EDC effects to improve risk assessment and regulatory frameworks.