Hydrolyzed pearl improves mitochondrial function in rats with diminished ovarian reserve via modulation of the AMPK/SIRT1/PGC-1α axis

To investigate whether hydrolyzed pearl improves mitochondrial function in rats with DOR through modulation of the AMPK/SIRT1/PGC-1α axis. Fifty-four female SD rats were randomly divided: 9 as normal controls, and 45 received oral tripterygium glycosides (50 mg/kg/d) for 21 days to induce DOR. After successful modeling, DOR rats were randomized into five groups (n = 9 each): model, estradiol valerate (0.09 mg/kg), and low-, medium-, and high-dose HP (0.0315, 0.063, and 0.126 g/kg, respectively). Following a 3-week intervention, body weight, estrous cycles, and ovarian index were assessed. Ovarian histomorphology was evaluated by HE staining. Serum FSH, LH, E 2 , AMH, and INHB levels were quantified via ELISA. Mitochondrial ultrastructure was observed by TEM; ovarian ROS levels, mitochondrial membrane potential (MMP), and ATP production were measured by flow cytometry, JC-1 staining, and spectrophotometry, respectively. AMPK, SIRT1, and PGC-1α expression was detected by Western blotting and qRT-PCR. Compared with the model group, HP significantly improved general condition, increased body weight and ovarian index, and partially restored estrous cyclicity. Ovarian morphology and follicular development were markedly enhanced. Serum FSH and LH levels were reduced, while E 2 , AMH, and INHB were elevated in all treatment groups. High-dose HP significantly improved mitochondrial function-related indicators: ROS levels were significantly reduced (P < 0.001 ), MMP was significantly increased ( P < 0.0001 ), and ATP production was significantly enhanced (P < 0.0001 ). Furthermore, AMPK, SIRT1, and PGC-1α expression was significantly upregulated at both protein and mRNA levels in treatment groups. Hydrolyzed pearl ameliorates estrous cycle irregularities and restores serum sex hormone balance in DOR rats, promotes follicular development, and improves mitochondrial structure and function. These effects may be mediated through stimulation of the AMPK/SIRT1/PGC-1α axis.