Adipose-derived regenerative cells attenuate diminished ovarian reserve in a rat model: evidence for the invol

Diminished ovarian reserve (DOR) involves reduced oocyte quantity and quality, leading to endocrine and reproductive dysfunction. Given the regenerative potential of adipose-derived regenerative cells (ADRCs), this study explored their therapeutic effect on DOR. The DOR model was induced in Sprague-Dawley rats using cyclophosphamide and busulfan, followed by intra-ovarian ADRCs injection. Following treatment, ovarian morphology, hormone levels, ferroptosis-related gene expression, oxidative stress markers, and fibrosis were assessed. Histological analysis revealed marked improvement in ovarian tissue and reduced fibrosis following ADRCs administration. The treatment significantly elevated serum anti-Müllerian hormone from 59.55 ± 24.59 to 147.40 ± 24.75 pg/mL (p < 0.01) and estradiol from 5.66 ± 0.35 to 8.20 ± 0.39 pmol/L (p < 0.001), while the elevated follicle-stimulating hormone showed a downward trend. ADRCs upregulated ferritin light chain and glutathione peroxidase 4 (GPX4) mRNA expression to approximately 214.6% (p < 0.001) and 137.7% (p < 0.05) of the DOR group. Meanwhile, GPX4 protein level was increased and 4-hydroxynonenal-labeled lipid peroxidation was reduced. Reactive oxygen species and other related markers also showed varying degrees of recovery. These findings suggest that ADRCs injection may improve DOR, as shown by improvement in endocrine function, alleviation of oxidative stress, modulation of ferroptosis, and attenuation of fibrosis, warranting further investigation.