Cucumeropsis mannii seed oil mitigates bisphenol-A-induced sperm and hormonal damages in F1-generation of F0-exposed male rats: An in-vivo and in-silico analysis

Abstract

Exposure to endocrine-disrupting chemicals such as bisphenol A (BPA) has been linked to the sharp drop in male fertility observed worldwide. This study evaluates the protective benefits of Cucumeropsis mannii seed oil (CMSO) against BPA-induced transgenerational sperm indices and reproductive hormone disruptions in rats. Twenty-four F0-male rats (aged 4–5 weeks) were randomly assigned to six groups (n = 4 each) after CMSO characterization for flavonoids. Group A received 1 ml of olive oil. Group B received 100 mg/kg body weight (BW) of BPA whereas Group C had a BW of 7.5 ml/kg CMSO. Groups D, E, and F were administered 100 mg/kg_BW of BPA in addition to 7.5, 5.0, and 2.5 ml/kg_BW of CMSO, respectively. After two weeks of treatment, four mature female rats were introduced to each group and allowed to stay together with male rats for seven days to confirm mating. Thereafter, the pregnant female rats were separated from the male according to their groups and allowed to give birth after 21 days of gestation period. At six weeks, the F1-male rats were isolated from each group and sacrificed for biochemical analysis. In-silico, CMSO flavonoids were assessed for drug-likeness and oral absorbability, followed by molecular docking to study their androgen receptor targeting mechanisms. Results showed that total flavonoids were 17.3652 ± 8.85 g/100 g. In-vivo, BPA significantly (p < 0.005) dysregulated sperm indices and male fertility hormones in F1 rats, but co-administration with CMSO restored these dysregulations in F1 rats. In-silico, the druglike molecules exhibited stronger binding affinities (−6.2 to −8.5 kcal/mol) for the androgen receptor than BPA (−6.1 kcal/mol) within the binding pockets. We postulated that CMSO mitigates transgenerational sperm indices and male fertility hormone disruption in F1 male offspring following F0 male exposure to BPA perhaps by utilizing androgen receptor signaling.