Doctoral Thesis
Molecular Mechanisms of Natural Products in Ovarian Development and Aging
Doctor of Philosophy (PhD), Murdoch University
2025
DOI:
https://doi.org/10.60867/00000075
Abstract
Ovarian aging critically impairs female reproductive function and contributes to systemic metabolic dysregulation. Natural compounds have demonstrated promise in delaying this decline in ovarian function. This study systematically evaluated the bidirectional regulatory effects of several natural products (Celastrol, Norgestimate, Thapsigargin, Cinobufagin, and Brefeldin A) on ovarian development, function, and aging. Focusing on Celastrol and Brefeldin A, we constructed a multi-level experimental model system, including 3-week-old and 12-month-old mouse models, porcine oocyte in vitro maturation systems, and granulosa cell culture models, to investigate the effects and mechanisms of these natural products both in vivo and at the cellular level.
The results demonstrated that Celastrol promotes follicular development, inhibits granulosa cell apoptosis, and delays ovarian aging by modulating the IRS1/SIRT signaling axis. At the same time, Brefeldin A suppresses follicular development and accelerates aging. For Norgestimate, Thapsigargin, and Cinobufagin, we used 3-week-old mouse models combined with HE staining and TUNEL assays to assess their effects on follicular development and apoptosis. The results revealed that Cinobufagin alleviates apoptosis and improves follicular function, whereas Norgestimate and Thapsigargin exhibit potential toxicities that impair ovarian function.
This study provides a reliable platform for mechanistic elucidation and toxicity evaluation of natural products by integrating complementary multi-level models. It highlights the dual roles of natural products in ovarian protection and aging intervention, clarifies their multi-target regulatory features and dose-dependent risks, and offers a scientific basis for future screening, mechanistic studies, and clinical translation of natural products.
Details
- Title
- Molecular Mechanisms of Natural Products in Ovarian Development and Aging
- Authors/Creators
- YAO Jiang
- Contributors
- Bin Ma (Supervisor) - Murdoch University, School of Medical, Molecular and Forensic SciencesFei Gao (Supervisor) - Agricultural Genomics Institute at ShenzhenPenghao Wang (Supervisor) - Harry Butler Institute
- Awarding Institution
- Murdoch University; Doctor of Philosophy (PhD)
- Identifiers
- 991005862493407891
- Murdoch Affiliation
- School of Medical, Molecular and Forensic Sciences; College of Environmental and Life Sciences
- Resource Type
- Doctoral Thesis
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