The findings suggest that CGA could serve as a promising non-hormonal therapy for premature ovarian failure (POF) , potentially avoiding some of the risks associated with conventional hormone treatments.
POF is a complex reproductive disorder caused by accelerated depletion of ovarian follicles, hormonal imbalances, and often oxidative damage. It can result from genetic, autoimmune, environmental, or iatrogenic factors, yet there is currently no cure. Hormone therapy is the standard treatment but may increase long-term health risks, including breast cancer. Oxidative stress, driven by excess reactive oxygen species (ROS), is a key driver of ovarian cell death. Antioxidants such as melatonin, resveratrol, and curcumin have shown protective effects in animal models. CGA—a compound abundant in coffee, fruits, and vegetables—has strong antioxidant and anti-inflammatory properties and has been shown to protect intestinal and neuronal cells from oxidative injury. Given the emerging role of gut microbiota in reproductive health, researchers hypothesized that CGA could both protect ovaries and restore microbial balance in POF.
A study (DOI: 10.48130/animadv-0025-0011) published in Animal Advances on 25 April 2025 by Shuang Liang & Yan Zhang’s team, Jilin University, improves ovarian function and restores gut microbiota balance in premature ovarian failure mice, highlighting the potential of CGA as a dual-action therapeutic strategy.
In this study, researchers evaluated the effects of CGA on POF in D-galactose-induced mice by combining physiological, histological, biochemical, and microbiological analyses. Body weight and ovarian organ coefficients were recorded, estrous cycles monitored via daily vaginal smears, and serum hormone levels along with ovarian Amh mRNA expression measured. Follicular development was assessed by counting different follicle stages and corpora lutea, oxidative stress markers including catalase (CAT), total antioxidant capacity (T-AOC), and malondialdehyde (MDA) were quantified, granulosa cell apoptosis detected by staining, and oxidative stress–related protein expression (p-Akt, Nrf2, HO-1) examined. Gut microbiota composition was profiled using 16S rDNA sequencing with diversity, taxonomic, and biomarker analyses, and correlations between bacterial taxa and POF-related parameters determined. Results showed that while CGA did not alter body weight or ovarian organ coefficient, high-dose CGA restored normal estrous cycles, improved hormone balance (lower FSH and LH, higher E2 and Amh mRNA), and enhanced ovarian reserve by increasing healthy follicles and corpora lutea while reducing atretic follicles. CGA significantly boosted CAT and T-AOC activity, reduced MDA content, and upregulated p-Akt, Nrf2, and HO-1, indicating activation of antioxidant defense pathways. Microbiota analysis revealed that CGA shifted beta diversity toward the healthy profile, reduced harmful taxa (CGA_873, UBA636, Robinsoniella, Escherichia, Enterobacterales_A, Enterobacteriaceae_A), and enriched beneficial genera (Allobaculum, Ileibacterium, Blautia_A), which were positively correlated with improved hormone levels, follicle counts, and antioxidant status, while harmful taxa were linked to ovarian damage markers. These findings indicate that CGA can simultaneously ameliorate ovarian dysfunction and gut dysbiosis in POF mice, underscoring its potential as a dual-action therapeutic candidate.
The dual action of CGA—protecting ovarian tissue and rebalancing gut microbiota—offers a novel therapeutic avenue for managing POF. As a natural compound found in commonly consumed foods, CGA presents a potential alternative or complementary strategy to hormone therapy, potentially reducing treatment risks. Its microbiome-modulating properties also highlight the importance of targeting gut health in reproductive disorders. While the current results are from animal models, they provide a mechanistic basis for exploring dietary or supplement-based interventions in human patients.
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References
DOI
10.48130/animadv-0025-0011
Original Source URL
https://doi.org/10.48130/animadv-0025-0011
Funding information
This research was supported by the Jilin Provincial Scientific and Technological Development Program (Grant No. YDZJ202301ZYTS355) and the College Student Innovation and Entrepreneurship Training Program at Jilin University (Grant No. 202310183341), China.
About Animal Advances
Animal Advances is an open-access journal which published by Maximum Academic Press in partnership with Nanjing Agricultural University. The journal is dedicated to delivering cutting-edge discoveries and progress in animal sciences to a diverse audience, encompassing scholars, academicians, and practitioners in the industry.