Ellagic acid alleviates nicotine-induced placental injury in pregnant rats: Histomorphometric and molecular evidence.

Maternal nicotine exposure during pregnancy is associated with placental dysfunction, oxidative stress, and impaired fetal development. Ellagic acid (EA), a naturally occurring polyphenolic compound with potent antioxidant properties, may protect placental tissues against nicotine-induced damage. This study investigated the protective effects of EA on placental histomorphometric alterations, oxidative stress, and apoptosis-related gene expression in nicotine-exposed pregnant rats. Twenty-four pregnant Wistar rats were randomly assigned to four groups (n = 6): control, EA (60mg/kg), nicotine (1mg/kg), and nicotine + EA. Treatments were administered orally from gestation day (GD) 0 to GD20. The H&E and PAS staining were used to evaluate placental architecture, trophoblast giant cells, and glycogen cell distribution. Oxidative stress biomarkers including MDA, CAT, TAC, SOD, and GPx were assessed. Expression levels of caspase-3, Bax, Bcl-2, and p53 genes were quantified using real-time PCR. Nicotine exposure significantly decreased the placental weight, diameter, and thickness characterized by disrupted placental architecture, changes in the thickness of placental layers, and the number of trophoblast giant cells (P<0.05). These changes were accompanied by increased lipid peroxidation, reduced antioxidant defense capacity, and dysregulation of apoptosis-related genes, including upregulation of caspase-3, Bax, and p53 and downregulation of Bcl-2. Co-administration of EA significantly attenuated these adverse effects by improving placental structural integrity, oxidative stress, and apoptosis-related genes expression (P<0.05). EA exerts significant protective effects against nicotine-induced placental injury, likely through its antioxidant and anti-apoptotic activities. These findings suggest that EA may represent a promising therapeutic strategy for mitigating placental toxicity associated with maternal nicotine exposure.