Yangjing Decoction Alleviates Diminished Ovarian Reserve in Rats by Activating the ESR1/PI3K/Akt/mTOR Pathway and Inhibiting GranulosaCell Apoptosis

PURPOSE: This research aimed to clarify the process by which Yangjing Decoction (YJD) controls ovarian function in diminished ovarian reserve (DOR) through the estrogen receptor 1 (ESR1)/phosphoinositide-3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway. METHODS: The DOR rat model was established. Serum concentrations of luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol (E2), anti-Müllerian hormone (AMH), and substance P (SP) were assessed using enzyme-linked immunosorbent assay (ELISA), and ovarian morphology was examined through hematoxylin-eosin staining. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blot were employed to measure the levels of ESR1, PI3K, Akt, mTOR, and apoptosis-related markers. Additionally, granulosa cells treated with triptolide (TPL) were treated with YJD, FSH, or camptothecin (CPT) to evaluate cell viability, apoptosis markers, and signaling pathway activation. RESULTS: YJD increased the number of primordial, primary, and preovulatory follicles in DOR rats, demonstrating improved ovarian morphology and follicular reserve. Moreover, YJD markedly elevated serum levels of LH, FSH, SP, AMH, and E2. YJD also inhibited apoptosis in ovarian cells, as indicated by decreased Caspase-3 and Bax levels and increased BCL-2 levels. At the cellular level, YJD reversed the reduction in granulosa cell viability, decreased apoptosis, and suppressed the ESR1/PI3K/Akt/mTOR pathway dysregulated by DOR. DISCUSSION: These results not only provide mechanistic insights into the therapeutic action of YJD but also highlight its potential application in reproductive medicine for women with diminished ovarian reserve. CONCLUSION: YJD appears to protect ovarian reserve function in DOR via altering the signaling pathway for ESR1/PI3K/Akt/mTOR.