Propolis mitigates histopathological alterations in the pituitary gland and reproductive system of female albino rats subjected to cadmium toxicity.

Background and aim: Cadmium (Cd) is a pervasive environmental toxin that disrupts endocrine function and induces oxidative damage in reproductive organs. Propolis (PRO), a resinous substance produced by bees, has garnered attention for its antioxidant and estrogenic properties. This study investigated the protective potential of PRO on the pituitary-ovarian-uterine axis in female rats subjected to Cd-induced toxicity.

Materials and methods: Thirty adult female albino rats were randomized into five groups (n = 6/group): Control (C), Cd-only (T0), and Cd plus PRO at 150, 300, and 500 mg/kg body weight (BW) (T1-T3, respectively). Cadmium chloride was administered orally at 5 mg/kg for 4 weeks. PRO was co-administered daily through gavage. At the proestrus stage, animals were euthanized for tissue collection. Vaginal cytology was used to confirm estrous stage. Histopathological examination of the ovary, uterus, and pituitary gland was performed using H&E staining. Serum estradiol (E2) and superoxide dismutase (SOD) activity were assessed to evaluate hormonal and oxidative responses. Morphometric measurements were statistically analyzed through one-way analysis of variance with Tukey's post hoc test.

Results: Cd exposure (T0) led to prolonged estrous cycles, ovarian atresia, uterine degeneration, and significant disruption of pituitary architecture, accompanied by reduced E2 and SOD levels (p < 0.05). PRO administration dose-dependently ameliorated these alterations. The highest PRO dose (T3) restored the histological architecture of all target organs to near-normal levels, significantly increased ovarian and uterine weight ratios, and elevated both E2 and SOD activity. Histomorphometric analysis confirmed increased follicle survival, thickened ovarian surface epithelium, and elevated interstitial cell counts. Pituitary endocrine cell counts and uterine gland numbers were also significantly higher in PRO-treated groups, particularly T3.

Conclusion: PRO supplementation at 500 mg/kg BW significantly attenuates Cd-induced reproductive and endocrine toxicity in female rats by restoring histological integrity and enhancing antioxidant and estrogenic responses. These findings suggest PRO as a promising candidate for mitigating heavy metal-induced reproductive dysfunction.