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Updated: Jun 5, 2025
Cell-Specific Paired Interrogation of the Mouse Ovarian Epigenome and Transcriptome
Published on: February 24, 2023
Triptolide exposure triggers ovarian inflammation by activating cGAS-STING pathway and decrease oocyte quality in
Si-Yao Cheng1, Yi-Fan Yang1, Ya-Long Wang2
1Medical College, Guangxi University, Nanning, Guangxi, 530004, China.
Abstract:
Triptolide (TPL), a prominent bioactive constituent derived from the Chinese herb Tripterygium wilfordii, exhibits diverse pharmacological effects such as anti-tumor and anti-immune properties. Despite its extensive clinical application for the treatment of arthritis and immune disorders, TPL has been associated with multiorgan toxicity, including adverse effects on the female reproductive system. However, the precise mechanisms underlying TPL-induced ovarian damage remain poorly understood. In this study, employing a mouse toxicological model, exposure to TPL was observed to result in decreased ovarian coefficient and fertility. Subsequent research demonstrated TPL exposure affected mitochondrial function, increased mitochondrial outer membrane permeability, resulted in mtDNA releasing into the cytoplasm. These events subsequently activated cGAS-STING pathway, leading to ovarian inflammation. Furthermore, TPL exposure has been found to disrupt the meiotic maturation of oocytes, which is mechanistically associated with suboptimal morphology of spindle and microtubule organizing centers (MTOCs). This association has been further confirmed through the use of reduced representation bisulfite sequencing (RRBS). In conclusion, our study demonstrates that TPL exposure can hinder follicular development, resulting in ovarian inflammation and reduced oocyte quality.
Insights
Triptolide (TPL) causes ovarian damage by affecting mitochondrial function and activating inflammation pathways. This leads to reduced fertility and oocyte quality, hindering follicular development.
Area of Science:
- Toxicology
- Reproductive Biology
- Molecular Biology
Background:
- Triptolide (TPL), from Tripterygium wilfordii, has anti-tumor and anti-immune uses.
- TPL causes multiorgan toxicity, including female reproductive system damage.
- Mechanisms of TPL-induced ovarian damage are not well understood.
Purpose of the Study:
- Investigate the mechanisms of TPL-induced ovarian toxicity.
- Evaluate the impact of TPL on ovarian function and oocyte quality.
- Identify molecular pathways involved in TPL's reproductive side effects.
Main Methods:
- Mouse toxicological model for TPL exposure.
- Assessment of ovarian coefficient and fertility.
- Analysis of mitochondrial function, mtDNA release, and cGAS-STING pathway activation.
- Evaluation of oocyte meiotic maturation, spindle, and MTOC morphology.
- Reduced representation bisulfite sequencing (RRBS) for confirmation.
Main Results:
- TPL exposure decreased ovarian coefficient and fertility in mice.
- TPL disrupted mitochondrial function, leading to mtDNA release and cGAS-STING pathway activation.
- Ovarian inflammation and follicular development hindrance were observed.
- TPL impaired oocyte meiotic maturation, affecting spindle and MTOCs.
Conclusions:
- TPL induces ovarian damage through mitochondrial dysfunction and inflammatory pathways.
- Impaired follicular development and reduced oocyte quality are key consequences of TPL exposure.
- Understanding these mechanisms is crucial for managing TPL's reproductive toxicity.
