Toxic Effects of Benzo[a]pyrene on Pancreatic Development and Function in Offspring Rats
This study investigated the toxic effects of intrauterine benzo[a]pyrene (BaP) exposure on pancreatic development and glucose metabolism in first-generation offspring rats. Pregnant Wistar rats were randomly divided into control and treatment groups receiving 200, 800, or 1600 μg·kg−1 BaP via daily oral gavage during gestation until delivery. Pancreatic histology was assessed in offspring at postnatal day 2 and week 12. Protein and mRNA expression of pancreatic duodenal homeobox-1 (PDX-1) and mitochondrial transcription factor A (TFAM) were quantified. Intraperitoneal glucose tolerance tests (IPGTT) and insulin tolerance tests (IPITT) were performed at week 12. Results showed that exposure to 800 and 1600 μg·kg−1 BaP caused dose-dependent pancreatic damage, with more severe islet morphological disruption and reduced islet area, which did not improve with age. PDX-1 and TFAM expression levels decreased in a dose-dependent manner at both time points. At week 12, the 1600 μg·kg−1 group exhibited pre-diabetic symptoms, including elevated blood glucose and insulin levels, and impaired glucose tolerance and insulin sensitivity. These findings indicate that intrauterine BaP exposure leads to persistent pancreatic developmental impairment and glucose metabolism disorders, potentially mediated by downregulation of PDX-1 and TFAM, with no recovery over time.