Sodium benzoate induces reproductive toxicity via hormonal disruption, ovarian damage and altering kisspeptin/RFRP-3 expression.

Sodium benzoate (SB) is a widely used food preservative; however, it has been shown to exert dose-dependent reproductive toxicity. In this study, we investigated its effects on the female reproductive axis. Sprague-Dawley rats (n = 30) were assigned to six groups (n = 5 each); the control group received distilled water, while treatment groups administered SB at doses of 10, 50, 100, 500 and1000 mg/kg orally for 90 days (sub-chronic exposure). Body and ovarian weights, biochemical parameters, protein content, hormonal profile, histology and central neuropeptides; kisspeptin (KP) and RFRP-3 were assessed. We confirmed that SB exposure altered reproductive axis by impairing ovarian health as evidenced by oxidative stress, decreased antioxidants and protein content, reduced follicular number and the consequent presence of atretic follicles. Low estradiol and FSH levels coupled with elevated LH levels were observed. Centrally, kisspeptin was significantly reduced, whereas RFRP-3 showed a steady increase in relation to SB concentrations. These imbalances contributed to irregular estrous cyclicity, decreased ovarian volume and lower ovarian weight, as observed in SB groups. Our findings indicate that SB intake can substantially alter the structural and molecular components of the HPG axis and directly induce ovarian toxicity. Therefore, it is important to minimize the long-term consumption of processed foods and complement them with more convenient and readily available natural dietary choices.