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Culture and Co-Culture of Mouse Ovaries and Ovarian Follicles
Published on: March 17, 2015
Triptolide exposure induces oxidative stress and decreases oocyte quality in mouse
Qian-Qian Hao1, Zhi-Ran Xu2, Han Nie1
1Medical College, Guangxi University, Nanning, Guangxi, 530004, China.
Abstract:
Triptolide is a major active ingredient isolated from the traditional Chinese medicine Tripterygium wilfordii, which has anti-inflammatory, anti-cancer, and immunomodulatory effects. However, in clinical studies, triptolide has toxic side effects on the heart, kidney, liver and reproductive organs. With respect to female reproductive toxicity, damaging effects of triptolide on the ovary have been reported, but it has remained unknown whether oocytes are affected by triptolide. Therefore, this study established a concentration gradient of triptolide exposure in mice using 0 (control), 30, 60, and 90 μg triptolide/kg body weight/day administered by gavage. Triptolide administration for 28 d reduced body weight and ovarian weight and affected the developmental potential of oocytes. The triptolide-treated group exhibited meiotic failure of oocytes due to impaired spindle assembly, chromosome alignment, and tubulin stability. Triptolide was also found to induce mitochondrial dysfunction, autophagy and early apoptosis, iron homeostasis, and abnormal histone modifications. These adverse effects could be associated with oxidative stress induced by triptolide. In conclusion, our findings suggest detrimental effects of triptolide on mouse oocytes and, thus, on female reproduction.
Insights
Triptolide, a compound from Tripterygium wilfordii, harms mouse oocytes, impacting female fertility. This study reveals triptolide
Area of Science:
- Reproductive Toxicology
- Molecular Biology
- Oocyte Biology
Background:
- Triptolide, from Tripterygium wilfordii, has therapeutic potential but exhibits reproductive toxicity.
- Oocyte-specific toxicity of triptolide remains poorly understood.
Purpose of the Study:
- To investigate the effects of triptolide on mouse oocyte quality and developmental potential.
- To elucidate the molecular mechanisms underlying triptolide-induced oocyte damage.
Main Methods:
- Mice were administered varying concentrations of triptolide (0, 30, 60, 90 μg/kg/day) for 28 days.
- Ovarian and body weights were measured; oocyte meiotic spindle assembly, chromosome alignment, and tubulin stability were assessed.
- Mitochondrial function, autophagy, apoptosis, iron homeostasis, and histone modifications were analyzed.
Main Results:
- Triptolide exposure reduced body and ovarian weights.
- Impaired spindle assembly, chromosome alignment, and tubulin stability led to meiotic failure in oocytes.
- Triptolide induced mitochondrial dysfunction, autophagy, apoptosis, altered iron homeostasis, and abnormal histone modifications, potentially via oxidative stress.
Conclusions:
- Triptolide exerts detrimental effects on mouse oocytes, compromising their developmental potential.
- These findings highlight triptolide's adverse impact on female reproductive health.
- Oxidative stress may be a key mechanism in triptolide-induced oocyte toxicity.
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