Ameliorative Role of <i>Phoenix dactylifera</i> Seeds Against Cadmium‐Induced Ovarian Toxicity in Rats: The Role of Low‐Dose Gamma Radiation

Cadmium exposure is a known disruptor of ovarian redox homeostasis and steroidogenesis, with clinically relevant implications for fertility and pregnancy outcomes. We hypothesized that date seed extract (DS), rich in antioxidant constituents, and low-dose gamma radiation (LDR) could synergistically counteract Cd-induced ovarian toxicity. (1) To assess whether DS and/or low-dose γ-radiation mitigate Cd-induced oxidative stress, inflammatory signaling, and impairment of steroidogenesis; (2) to determine whether the combination of DS + LDR offers superior protection relative to single treatments; and (3) to evaluate whether biochemical improvements translate to preservation of ovarian histology. The present study highlights the combinatorial approach (DS + LDR) as a potential, novel intervention for reducing Cd-associated gonadotoxicity. Forty-eight female Swiss albino rats were allocated to eight groups (n = 6): Control; DS; R; DS + R; Cd; Cd + DS; Cd + R; Cd + DS + R. Treatments were administered for 21 days (DS) and 2 weeks (Cd exposure) with ongoing γ-radiation where indicated. Outcomes included: (i) oxidative stress markers (SOD, GSH); (ii) steroidogenic axis components (StAR, CYP11A1, 3β-HSD, 17β-HSD) at the ovarian level; (iii) hormonal profiles (e.g., estrogen, progesterone, and relevant gonadotropins); (iv) inflammatory signaling (NF-κβ); and (v) histopathology of ovarian sections. Cd exposure caused a significant decline in ovarian antioxidants (SOD, GSH) and a reduction in steroidogenic enzyme expression, accompanied by hormonal disturbances and prominent NF-κβ-driven inflammatory changes. Histologically, Cd induced cortical and follicular disruption with increased degenerative changes. DS and LDR mitigated these effects, with the combination DS + LDR showing the most robust rescue: antioxidant defenses and steroidogenic enzyme expression nearly normalized, hormonal levels stabilized, NF-κβ signaling reduced, and ovarian architecture preserved. Statistical significance was achieved for most endpoints (p < 0.05) and trends supported additive or synergistic benefits for DS + LDR. The combination of DS and low-dose γ-radiation offers superior protection against Cd-induced ovarian toxicity by restoring redox balance, downregulating inflammatory pathways, normalizing steroidogenesis, and preserving ovarian histology. These findings support further exploration of DS + R as a potential therapeutic strategy to mitigate heavy metal-related reproductive damage.