Procyanidin c-1 intervention on bisphenol a-induced reproductive dysfunction in male mice

Exposure to bisphenol A (BPA), an endocrine-disrupting chemical, is known to result in reproductive dysfunction. Procyanidin C-1 (PCY-1), derived from grape seed extract, is a potent antioxidant with antiviral, antimelanogenic, and immunostimulatory properties. This study determined the effect of PCY-1 intervention in mitigating the adverse effect of BPA on sperm parameters, testicular morphology, serum levels of testosterone, oestradiol and LH, and the testicular expression of genes related to apoptosis (Bax and Bcl-2), mitochondria (Mfn1 and Opa1) and oxidative stress (Sod1 and Gpx1) in C57BL/6NTac mature adult and aged mice. The mice were divided into four groups: control group (H2O), BPA-induced group (BPA), PCY-1-only treatment (PCY-1) and co-administration of PCY-1 and BPA (PCY-1+BPA). The dose for BPA is 15 mg/kg body weight, and the dose for PCY-1 is 20 µg/kg body weight. The treatments were administered daily via oral gavage for a duration of 35 days. Intervention of PCY-1 in BPA-induced mature adult mice exhibited body weight loss and significant increases in the testes coefficient. PCY-1 intervention also showed increase on sperm concentration and a significant decrease on abnormal sperm morphology in BPA-induced mature adult mice. Histological examination of testes also showed a significant enhancement of the diameter of seminiferous tubules in the PCY-1 intervention BPA-induced mature adult mice. The PCY-1 intervention had significant effects on testosterone and LH levels, leading to a decrease, while oestradiol levels increased in mature adult mice. The PCY-1 intervention in BPA-induced mature adult mice decreased Bax gene expression and increased Bcl-2 gene expression. The PCY-1 intervention also downregulated Mfn1, Opa1 and Sod1 gene expression. In the BPA- induced aged mice, PCY-1 intervention significantly increased body weight and seminal vesicle coefficient. The intervention of PCY-1 in BPA-induced aged mice also revealed an improved testicular and sperm parameter with a lower percentage of abnormal sperms and greater seminiferous tubules width and epithelial height. In term of the hormonal analysis, only a significant reduction in oestradiol levels was observed in the intervention of PCY-1 in BPA-induced aged mice. In addition, no significant results were obtained from the measurement of antioxidant levels in the BPA-induced aged mice with PCY-1 intervention. The intervention of PCY-1 in BPA-induced aged mice also showed a decrease in the Bax gene expression and an increase in the Bcl-2 gene expression, while the Mfn1, Opa1, Sod1 and Gpx1 genes showed a significant upregulation. In conclusion, PCY-1 was able to attenuate the negative effects of BPA on the reproductive parameters of mature adult and aged mice, possibly via anti- apoptotic mechanisms. The hypothesis that PCY-1 protects the mature and ageing male reproductive system from the harmful effects of BPA is therefore accepted.