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Food and Chemical Toxicology

Food and Chemical Toxicology

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

Published:11 December 2024 DOI: 10.1016/j.fct.2024.115201 PMID: 39672454
Si-Yao Cheng,?Yi-Fan Yang,?Ya-Long Wang,?Zhao-Ping Yue,?Yan-Zhu Chen,?Wen-Ke Wang,?Zhi-Ran Xu,?Lin-Feng Li,?Hao Shen,?Zhi-Min Qi,?Chang-Long Xu,?Yu Liu

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.

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Materials
Procduct Name CAS Molecular Formula Supplier Price
Chorionic Gonadotropin 9002-61-3 C17H28 242 suppliers $89.90-$3320.00

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