Smart-seq2 Technology Reveals a Novel Mechanism That Zearalenone Inhibits the In Vitro Maturation of Ovine Oocytes by Influencing TNFAIP6 Expression

Li, Zongshuai; Liu, Yali; Ma, Tian; Lv, Chen; Li, Yina; Duan, Hongwei; Zhao, Xingxu; Wang, Jianlin; Zhang, Yong

doi:10.3390/toxins15100617

Cited by 2 publications

(2 citation statements)

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“…It has a stable structure, is not easily degradable, is widely distributed, can be present at any stage of crop processing, and easily contaminates various grains [ 4 , 5 , 6 ]. It poses a threat to the livestock breeding industry (pigs, sheep, and cows) [ 7 , 8 , 9 , 10 ], as well as human reproductive health. Therefore, it is of great importance to determine the mechanism of toxicity of ZEN and screen for effective antagonistic drugs.…”

Section: Introductionmentioning

confidence: 99%

“…The combination of Smart-seq2 technology and preliminary results of this study showed that ZEN could increase oxidative stress, interfere with the spindle assembly and cell autophagy, and ultimately inhibit ovine oocyte maturation by affecting the expression of genes related to apoptosis, oxidative stress, autophagy, oocyte maturation, and spindle assembly [ 10 ]. Therefore, a constantly updated natural plant compound library and the screening of antagonistic drugs were combined in this study, focusing on two types of substances: antioxidants and autophagy inhibitors.…”

Section: Introductionmentioning

confidence: 99%

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Screening and Mechanism Study of Three Antagonistic Drugs, Oxysophoridine, Rutin, and Phellodendrine, against Zearalenone-Induced Reproductive Toxicity in Ovine Oocytes

Li,

Ma,

Liu

et al. 2024

Antioxidants

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Zearalenone (ZEN) is a common fungal toxin with reproductive toxicity in various grains. It poses a serious threat to ovine and other animal husbandry industries, as well as human reproductive health. Therefore, investigating the mechanism of toxicity and screening antagonistic drugs are of great importance. In this study, based on the natural compound library and previous Smart-seq2 results, antioxidant and anti-apoptotic drugs were selected for screening as potential antagonistic drugs. Three natural plant compounds (oxysophoridine, rutin, and phellodendrine) were screened for their ability to counteract the reproductive toxicity of ZEN on ovine oocytes in vitro using quantitative polymerase chain reaction (qPCR) and reactive oxygen species detection. The compounds exhibited varying pharmacological effects, notably impacting the expression of antioxidant (GPX, SOD1, and SOD2), autophagic (ATG3, ULK2, and LC3), and apoptotic (CAS3, CAS8, and CAS9) genes. Oxysophoridine promoted GPX, SOD1, ULK2, and LC3 expression, while inhibiting CAS3 and CAS8 expression. Rutin promoted SOD2 and ATG3 expression, and inhibited CAS3 and CAS9 expression. Phellodendrine promoted SOD2 and ATG3 expression, and inhibited CAS9 expression. However, all compounds promoted the expression of genes related to cell cycle, spindle checkpoint, oocyte maturation, and cumulus expansion factors. Although the three drugs had different regulatory mechanisms in enhancing antioxidant capacity, enhancing autophagy, and inhibiting cell apoptosis, they all maintained a stable intracellular environment and a normal cell cycle, promoted oocyte maturation and release of cumulus expansion factors, and, ultimately, counteracted ZEN reproductive toxicity to promote the in vitro maturation of ovine oocytes. This study identified three drugs that antagonize the reproductive toxicity of ZEN on ovine oocytes, and compared their mechanisms of action, providing data support and a theoretical basis for their subsequent application in the ovine breeding industry, reducing losses in the breeding industry, screening of ZEN reproductive toxicity antagonists and various toxin antagonists, improving the study of ZEN reproductive toxicity mechanisms, and even protection of human reproductive health.

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