Nano-Encapsulated Curcumin Improves Ovarian and Uterine Recovery from Cadmium Toxicity in Rats

Cadmium (Cd) is a ubiquitous environmental toxicant that causes adverse effects on female reproductive organs. Curcumin (Cm) has potent antioxidant and anti-inflammatory properties, but it has low solubility and bioavailability. The present study aimed to evaluate and compare the protective effects of native Cm and polycaprolactone/polyvinyl alcohol-based curcumin nanoparticles (PCL/PVA/Cm NPs) against Cd-induced ovarian and uterine toxicity in female rats through histopathological, semi-quantitative, and morphometric analyses.

Forty-eight adult female rats were randomly assigned to six groups (n = 8/group): control, Cd, Cm, Cd + Cm, PCL/PVA/Cm NPs, and Cd + PCL/PVA/Cm NPs. Treatments were given orally for four weeks. Ovarian and uterine tissues were collected at the end of the experimental period for histopathological analysis, semi-quantitative histological scoring, and morphometric evaluation.

Cd exposure induced marked ovarian and uterine histopathological changes, including follicular atresia, degeneration of corpora lutea, vascular congestion, thinning of the endometrial epithelium, glandular atrophy and inflammatory cell infiltration, and reduced endometrial and myometrial thickness. Interestingly, treatment with free Cm maintained normal granulosa cell proliferation and uterine morphology. Administration of Cm along with Cd revealed partial histological recovery compared with the group treated with Cd alone. On the other hand, PCL/PVA-encapsulated Cm showed the most significant histological improvements with signs of active folliculogenesis and normal uterine structure. Interestingly, the group treated with Cd + PCL/PVA/Cm NPs showed almost complete recovery of ovarian and uterine structure with histological scores comparable to those of the control groups.

The significant restoration of ovarian and uterine tissues and folliculogenesis in PCL/PVA/Cm NPs-treated animals could be attributed to the enhanced bioavailability and sustained release of Cm.

PCL/PVA/Cm NPs exhibited greater protective and restorative effects against Cd-induced reproductive toxicity than native Cm, indicating that nanoparticle-mediated delivery of curcumin may represent an effective strategy for protecting the female reproductive system against heavy metal-induced damage.