ABSTRACT 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.
Kayed et al. (Wed,) studied this question.