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Amelioration of obesity-induced testicular dysfunction and structural damage by ganoderma lucidum polysaccharides and
Li Yanhong1, Liang Wei1, Han Yunlin1
1NHC Key Laboratory of Comparative Medicine, National Human Diseases Animal Model Resource Center, National Center of Technology Innovation for animal model, Beijing 100021, China; Key Laboratory of Pathogen Infection Prevention and Control (Peking Union Medical College), Ministry of Education, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021, China.
Abstract:
Obesity is a global health crisis and a critical risk factor for male infertility, impairing testicular structure and function through hormonal imbalance and oxidative stress. Current therapeutic strategies are often unsatisfactory due to limited efficacy or adverse effects. This study investigated the protective effects and potential molecular mechanisms of Ganoderma lucidum (GL) polysaccharides and triterpenoids against testicular injury in high-fat diet-induced obese male rats. After 12-week GL intervention, reproductive function in obese male rats showed improvement: GL increased litter size, improved sperm motility, reduced sperm DNA fragmentation, and restored serum testosterone, inhibin B, and leptin levels. It also alleviated testicular histopathological damage, downregulated PPT1, and maintained vimentin expression. Notably, GL facilitated delayed fertility recovery and showed a trend toward improved cumulative reproductive success, although fixed-time pregnancy rates were not significantly changed. Mechanistically, GL is associated with enhanced Nrf2 pathway activity, increased SOD1, HO-1, NQO1, and GPX4 levels, and decreased MDA and ROS accumulation, thereby attenuating oxidative stress. It preserved mitochondrial integrity, suppressed germ cell apoptosis (downregulating Bax and caspase-3, upregulating Bcl-2), and promoted cell proliferation. These findings indicate that GL polysaccharides and triterpenoids effectively ameliorate obesity-induced testicular dysfunction, and these beneficial effects are associated with Nrf2-mediated antioxidant responses, mitochondrial homeostasis, apoptosis regulation, and hormonal balance. GL may serve as a promising candidate for obesity-related male infertility.
Insights
Ganoderma lucidum (GL) combats male infertility caused by obesity. GL improves reproductive function and sperm health by reducing oxidative stress and restoring hormonal balance in obese rats.
Area of Science:
- Reproductive Biology
- Endocrinology
- Toxicology
- Natural Product Chemistry
Background:
- Obesity is a significant global health issue linked to male infertility, causing testicular dysfunction via hormonal imbalance and oxidative stress.
- Existing treatments for obesity-related male infertility have limitations in efficacy and potential adverse effects.
- Ganoderma lucidum (GL), known for its medicinal properties, has not been fully explored for its effects on male reproductive health in obesity models.
Purpose of the Study:
- To investigate the protective effects of Ganoderma lucidum (GL) polysaccharides and triterpenoids against testicular injury in male rats with diet-induced obesity.
- To elucidate the molecular mechanisms underlying GL's potential therapeutic actions on obesity-related male infertility.
Main Methods:
- Male rats were fed a high-fat diet to induce obesity, followed by a 12-week intervention with Ganoderma lucidum (GL).
- Evaluated reproductive parameters including litter size, sperm quality (motility, DNA fragmentation), and serum hormone levels (testosterone, inhibin B, leptin).
- Assessed testicular histopathology, oxidative stress markers (SOD1, HO-1, NQO1, GPX4, MDA, ROS), mitochondrial integrity, apoptosis markers (Bax, caspase-3, Bcl-2), and Nrf2 pathway activation.
Main Results:
- GL intervention significantly improved reproductive function in obese rats, increasing litter size, sperm motility, and restoring key hormone levels.
- GL treatment reduced testicular damage, decreased sperm DNA fragmentation, and attenuated oxidative stress by enhancing antioxidant enzyme activity and reducing reactive oxygen species (ROS).
- Mechanistically, GL promoted Nrf2 pathway activation, preserved mitochondrial integrity, regulated apoptosis, and maintained vimentin expression, contributing to improved testicular function.
Conclusions:
- Ganoderma lucidum (GL) effectively ameliorates obesity-induced testicular dysfunction and infertility in male rats.
- The beneficial effects of GL are attributed to its antioxidant properties via the Nrf2 pathway, improved mitochondrial function, apoptosis regulation, and hormonal balance.
- GL presents a promising natural therapeutic candidate for managing male infertility associated with obesity.