Effects of zinc and manganese supplementation on ovarian function and mTOR gene expression in a rat model of polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is a complex endocrine disorder with multifactorial pathophysiology involving oxidative stress, insulin resistance, and dysregulated ovarian signaling pathways. Although zinc (Zn) and manganese (Mn) are essential trace elements with established roles in reproductive health, their individual and comparative effects on ovarian molecular pathways remain poorly characterized. This study investigated whether Mn supplementation could ameliorate PCOS-induced ovarian dysfunction in association with alterations in mechanistic target of rapamycin (mTOR) gene expression and examined the comparative effects with Zn status. One hundred fifty adult female Wistar rats were divided into healthy and PCOS-induced groups (estradiol valerate, 4 mg, 4 weeks). Each group received five dietary treatments for 6 weeks: basal diet, Zn-deficient diet, Zn-supplemented diet (200 mg/kg), Mn-deficient diet, or Mn-supplemented diet (100 mg/kg). Serum estradiol and testosterone were measured by ELISA. Ovarian histomorphology was evaluated, and mTOR gene expression was quantified by real-time PCR. Two-way ANOVA was used to assess main effects and interactions, and Pearson correlation analysis was performed to examine relationships between variables. PCOS induction significantly decreased estradiol (88.58 vs. 97.83 pmol/L, P < 0.05), increased testosterone (0.050 vs. 0.032 ng/mL, P = 0.047), and downregulated mTOR expression (1.09 vs. 1.54, P = 0.020). Mn supplementation (100 mg/kg) significantly elevated estradiol (124.96 vs. 62.19 pmol/L, P < 0.05), reduced testosterone (0.042 vs. 0.040 ng/mL), and showed a tendency to increase mTOR expression (1.24 vs. 1.00). Zn deficiency negatively affected several reproductive and endocrine indices (notably elevating testosterone and reducing ovarian follicle reserves), though this effect was not uniform across all measured parameters. Significant interactions between physiological status and dietary treatment were observed for most variables ( P < 0.05). mTOR expression correlated positively with estradiol ( r = 0.72, P < 0.01) and negatively with testosterone ( r = − 0.68, P < 0.01). Mn supplementation was associated with protective effects against PCOS-induced ovarian dysfunction, likely through modulation of the mTOR signaling pathway. The comparative effects with Zn status highlight the importance of comprehensive trace element assessment. These findings suggest that Mn supplementation may represent a promising nutritional strategy for PCOS management.