A metabolomic approach to study triptolide-induced ovarian damage in rats

Zhou, Feng; Zhong, Lu Lu; Tan, Yi; Liu, Li; Pei, Gang

doi:10.1016/j.tox.2022.153351

Cited by 5 publications

(2 citation statements)

References 54 publications

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“…As shown above, ovarian RAS genes including Agt were also upregulated in the aged NP ovary ( Section 2.1 ). On the other hand, expression of Ptgds inhibits granulosa cell proliferation in the adult ovary [ 40 ] while PGD2 synthesis increases in the rat ovary in response to the toxicant triptolide [ 41 ]. Similarly, the dipeptidase Dpep1 enzyme converts leukotriene-D4 to -E4 and also acts as a neutrophil adhesion molecule promoting inflammation [ 42 ].…”

Section: Resultsmentioning

confidence: 99%

Transcriptomic Analysis of the Aged Nulliparous Mouse Ovary Suggests a Stress State That Promotes Pro-Inflammatory Lipid Signaling and Epithelial Cell Enrichment

Chacón,

Mounieres,

Ampuero

et al. 2023

IJMS

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Ovarian cancer (OC) incidence and mortality peaks at post-menopause while OC risk is either reduced by parity or increased by nulliparity during fertile life. The long-term effect of nulliparity on ovarian gene expression is largely unknown. In this study, we describe a bioinformatic/data-mining analysis of 112 coding genes upregulated in the aged nulliparous (NP) mouse ovary compared to the aged multiparous one as reference. Canonical gene ontology and pathway analyses indicated a pro-oxidant, xenobiotic-like state accompanied by increased metabolism of inflammatory lipid mediators. Up-regulation of typical epithelial cell markers in the aged NP ovary was consistent with synchronized overexpression of Cldn3, Ezr, Krt7, Krt8 and Krt18 during the pre-neoplastic phase of mOSE cell cultures in a former transcriptome study. In addition, 61/112 genes were upregulated in knockout mice for Fshr and for three other tumor suppressor genes (Pten, Cdh1 and Smad3) known to regulate follicular homeostasis in the mammalian ovary. We conclude that the aged NP ovary displays a multifaceted stress state resulting from oxidative imbalance and pro-inflammatory lipid signaling. The enriched epithelial cell content might be linked to follicle depletion and is consistent with abundant clefts and cysts observed in aged human and mouse ovaries. It also suggests a mesenchymal-to-epithelial transition in the mOSE of the aged NP ovary. Our analysis suggests that in the long term, nulliparity worsens a variety of deleterious effects of aging and senescence thereby increasing susceptibility to cancer initiation in the ovary.

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Section: Resultsmentioning

confidence: 99%

Transcriptomic Analysis of the Aged Nulliparous Mouse Ovary Suggests a Stress State That Promotes Pro-Inflammatory Lipid Signaling and Epithelial Cell Enrichment

Chacón,

Mounieres,

Ampuero

et al. 2023

IJMS

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“…However, plenty of studies have exhibited severe reproductive system toxicity in TP-treated animals and patients 5 , 6 . TP can significantly induce ovarian damage, resulting in follicular atresia, a decrease in the number of corpus luteum and in the gonad index, and the destruction of ovarian microstructure 7 , 8 . Oxidative stress is one of the core molecular mechanisms involved in the toxicity of TP, and has been demonstrated to be tightly associated with follicular atresia and ovulation disorders, including premature ovarian failure (POF) and polycystic ovary syndrome (PCOS) 9 , 10 .…”

Section: Introductionmentioning

confidence: 99%

XinJiaCongRongTuSiZiWan protects triptolide-induced rats from oxidative stress injury via mitophagy mediated PINK1/Parkin signaling pathway

Jin,

Di-si,

Ke-ming

2024

Acta Cir. Bras.

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Purpose: XinJiaCongRongTuSiZiWan (XJCRTSZW) is a traditional Chinese medicine compound for invigorating the kidney, nourishing blood, and promoting blood circulation. This study aimed to explore the effect of XJCRTSZW on triptolide (TP)-induced oxidative stress injury. Methods: Adult female Sprague-Dawley rats and human ovarian granulosa cell lines were treated with TP and XJCRTSZW. Hematoxylin and eosin staining, enzyme-linked immunosorbent assay, flow cytometry, CCK-8, JC-1 staining, transmission electron microscopy, reverse transcription-quantitative polymerase chain reaction, and Western blotting were performed in this study. Results: XJCRTSZW treatment observably ameliorated the TP-induced pathological symptoms. Furthermore, XJCRTSZW treatment observably enhanced the TP-induced reduction of estradiol, anti-Mullerian hormone, progesterone, superoxide dismutase, ATP content, mitochondrial membrane potential, p62, and Hsp60 mRNA, and protein levels in vivo and in vitro ( p < 0.05). However, TP-induced elevation of follicle stimulating hormone and luteinizing hormone concentrations, malondialdehyde levels, reactive oxygen species levels, apoptosis rate, mitophagy, and the mRNA and protein expressions of LC3-II/LC3-I, PTEN-induced kinase 1 (PINK1), and Parkin were decreased ( p < 0.05). In addition, XJCRTSZW treatment markedly increased cell viability in vitro ( p < 0.05). Conclusions: XJCRTSZW protects TP-induced rats from oxidative stress injury via the mitophagy-mediated PINK1/Parkin pathway.

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Recent advances in the pharmacological applications and liver toxicity of triptolide

Cui

Yue

et al. 2023

Chemico-Biological Interactions

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A metabolomic approach to study triptolide-induced ovarian damage in rats

Cited by 5 publications

References 54 publications

Transcriptomic Analysis of the Aged Nulliparous Mouse Ovary Suggests a Stress State That Promotes Pro-Inflammatory Lipid Signaling and Epithelial Cell Enrichment

Transcriptomic Analysis of the Aged Nulliparous Mouse Ovary Suggests a Stress State That Promotes Pro-Inflammatory Lipid Signaling and Epithelial Cell Enrichment

XinJiaCongRongTuSiZiWan protects triptolide-induced rats from oxidative stress injury via mitophagy mediated PINK1/Parkin signaling pathway

Recent advances in the pharmacological applications and liver toxicity of triptolide

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