Triptolide exposure triggers ovarian inflammation by activating cGAS-STING pathway and decrease oocyte quality in...

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.