Abstract
Background:
Cadmium (Cd) is a pervasive environmental toxicant associated with female reproductive dysfunction through endocrine disruption and oxidative stress. Strategies that enhance antioxidant bioavailability may improve therapeutic efficacy against heavy metal–induced ovarian damage.

Aim:
To investigate the protective efficacy of polycaprolactone/polyvinyl alcohol–loaded curcumin nanoparticles (PCL/PVA/Cm NPs) against CdCl₂-induced reproductive toxicity in female rats, focusing on hormonal modulation and hypothalamic–pituitary–ovarian axis gene expression.

Methods:
Forty-eight adult female rats were allocated into six groups: control, CdCl₂, curcumin, CdCl₂+curcumin, PCL/PVA/Cm NPs, and CdCl₂+PCL/PVA/Cm NPs. Body and reproductive organ weight, serum GnRH, FSH, LH, estradiol, progesterone, and prolactin levels were assessed after 4 weeks. Ovarian (LHR, FSHR, aromatase) and pituitary (LHβ, FSHβ, CYP450, PRL) gene expression levels were quantified.

Results:
The results revealed that CdCl₂ exposure significantly reduced body, ovarian, and uterine weights and suppressed GnRH, FSH, LH, estradiol, and progesterone levels while elevating prolactin levels. Ovarian and pituitary reproductive gene expression was markedly downregulated. Curcumin partially reversed these effects; however, nanoformulated curcumin produced significantly greater restoration, normalizing hormonal profiles and gene expression patterns to near-control values.

Conclusion:
The nano-encapsulation markedly enhances curcumin bioefficacy, effectively restoring endocrine balance and molecular signaling within the reproductive axis. PCL/PVA/Cm nanoparticles represent a promising nanotherapeutic strategy for mitigating cadmium-induced female reproductive toxicity.

Key words: Cadmium chloride; Curcumin nanoparticles; Endocrine disruption; Polycaprolactone; Polyvinyl alcohol.