Growth Hormone Reverses Cisplatin-Induced Ovarian Reserve Depletion in Mice: Transcriptomic Elucidation of Mitochondrial Metabolic Reprogramming and Protein Synthesis Regulation.

Diminished ovarian reserve (DOR) presents a formidable challenge for assisted reproduction technology, as affected patients typically exhibit reduced oocytes and embryos during in vitro fertilization and embryo transfer (IVF-ET), which may ultimately lead to compromised clinical pregnancy rate. Although growth hormone (GH) supplementation has shown clinical efficacy in improving the outcomes of IVF-ET, the precise molecular mechanisms underlying its ability to enhance ovarian reserve have remained poorly characterized. In this study, a cisplatin-induced DOR mice model was established via intraperitoneal cisplatin administration. GH was subsequently evaluated at four dose levels over a 21-day intervention period. Comprehensive assessments included quantitative follicular histomorphometry, serum hormone profiling, and whole-transcriptome analysis of ovarian tissue. GH treatment significantly increased the number of primary and secondary follicles in a dose-dependent manner (p < 0.05), while concurrently reducing atretic follicle counts in the medium- and high-dose GH groups compared to the DOR group (p < 0.05). Furthermore, GH treatment restored hormonal balance, characterized by decreased follicle-stimulating hormone (FSH) and increased estradiol (E2) and anti-müllerian hormone (AMH) levels (p < 0.05). Transcriptomic analysis revealed that differentially expressed genes (DEGs) between the DOR and negative control (NC) groups were primarily associated with mitochondrial energy metabolism and the reproductive endocrine system, with functional enrichment in ribosome biogenesis, oxidative phosphorylation, and thermogenesis. In contrast, DEGs between the high-dose GH and DOR groups were predominantly enriched in pathways related to immunity, mitochondrial function, protein synthesis, and extracellular matrix-receptor interactions. In conclusion, GH can restore the ovarian reserve in cisplatin-induced DOR mice in a dose-dependent manner, potentially by modulating the genetic networks involved in energy metabolism, oxidative homeostasis, and protein synthesis.