Evidence map›Paper›PMID 42352304›Full record

ArticleBiomolecules2026

Zearalenone Induces Gap Junction Damage in Ovine Ovarian Granulosa Cells by Upregulating GPR30 and Activating the Oxidative Stress-NLRP3 Inflammasome Axis.

Xiaoyun Pang, Dong Zhang, Hongwei Duan, Zhenxing Yan, Xianghong Du, Lujie Zhao, Jincheng Yang, Li Xue, Yanyan Wang, Yuxuan He

Abstract read
In one paragraph

Article in Biomolecules, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Xiaoyun PangCollege of Veterinary Medicine, Gansu Agricultural University, Lanzhou 730070, China.
Dong ZhangCollege of Veterinary Medicine, Gansu Agricultural University, Lanzhou 730070, China.
Hongwei DuanCollege of Veterinary Medicine, Anhui Agricultural University, Hefei 230036, China.
Zhenxing YanCollege of Veterinary Medicine, Gansu Agricultural University, Lanzhou 730070, China.
Xianghong DuCollege of Veterinary Medicine, Gansu Agricultural University, Lanzhou 730070, China.
Lujie ZhaoCollege of Veterinary Medicine, Gansu Agricultural University, Lanzhou 730070, China.
Jincheng YangCollege of Veterinary Medicine, Gansu Agricultural University, Lanzhou 730070, China.
Li XueCollege of Veterinary Medicine, Gansu Agricultural University, Lanzhou 730070, China.
Yanyan WangCollege of Veterinary Medicine, Gansu Agricultural University, Lanzhou 730070, China.
Yuxuan HeCollege of Veterinary Medicine, Gansu Agricultural University, Lanzhou 730070, China.ORCID 0000-0002-2136-9814

Funding

Foundation for Youth Doctor of Gansu Province 2021QB-026Gansu Agricultural University GAU-XKJS-2018-067Local Science and Technology Development (Gansu province) Guided by Central Government 03322026National Natural Science Foundation of China 31902339Scientific Research Start-up Funds for Openly-Recruited Doctors of Gansu Agricultural University 2017RCZX-13Youth Talent Program of "Fuxi" Gaufx-03Y02
6 · The paper itself

Abstract

Ovarian granulosa cells (GCs) ensure proper follicular development and oocyte maturation through gap-junction-mediated intercellular communication. Zearalenone (ZEA), a mycotoxin with estrogen-like activity, specifically targets and impairs ovarian function. Most existing studies have focused on ZEA-induced apoptosis in GCs, but whether ZEA disrupts gap junctions in ovarian GCs remains unclear. Therefore, the aim of this study was to investigate whether and how ZEA induces gap junction injury in ovine ovarian GCs, with a particular focus on the roles of G protein-coupled receptor 30 (GPR30), oxidative stress, and the NLRP3 inflammasome. In the present study, primary ovine ovarian GCs were isolated, cultured, and treated with different concentrations of ZEA to establish a gap junction injury model, and specific inhibitors/antagonists were used to investigate the underlying mechanisms. The results showed that ZEA decreased granulosa cell viability and significantly inhibited the expression of the gap junction proteins Connexin 43 (Cx43) and Connexin 37 (Cx37) in a concentration-dependent manner. ZEA treatment also significantly upregulated the expression of the NOD-like receptor familypyrindomain containing 3 (NLRP3) inflammasome-related proteins (NLRP3, ASC, Cleaved Caspase-1, and the downstream pro-inflammatory cytokine IL-1β) in a concentration-dependent manner. Pretreatment with the NLRP3-specific inhibitor MCC950 significantly reversed ZEA-induced downregulation of Cx43 and Cx37 and effectively blocked NLRP3 inflammasome activation, indicating that NLRP3 is a key target in ZEA-induced gap junction injury. Further experiments confirmed that ZEA treatment significantly increased oxidative stress levels in granulosa cells; pretreatment with the reactive oxygen species (ROS) scavenger N-acetylcysteine (NAC) restored the ZEA-induced downregulation of Cx43 and Cx37 and suppressed NLRP3 inflammasome activation, suggesting that ROS acts as an upstream regulator of NLRP3 inflammasome activation. Moreover, ZEA treatment altered GPR30 expression levels, and pretreatment with the GPR30 antagonist G15 effectively inhibited ZEA-induced ROS production, NLRP3 inflammasome activation, and downregulation of Cx43/Cx37, indicating that ZEA exerts its effects through functional activation of GPR30. Collectively, ZEA activates the GPR30 receptor, induces ROS accumulation in granulosa cells, and subsequently triggers NLRP3 inflammasome activation, ultimately leading to downregulation of Cx43 and Cx37 and gap junction dysfunction. This study reveals a previously unrecognized molecular mechanism by which ZEA induces gap junction injury in ovarian GCs, providing potential therapeutic targets and a theoretical basis for preventing ZEA-induced ovarian dysfunction and improving animal reproductive health.

Indexed as

Gap JunctionsGranulosa CellsInflammasomesNLR Family, Pyrin Domain-Containing 3 ProteinOxidative StressReceptors, G-Protein-CoupledZearalenoneAnimalsCells, CulturedConnexin 43FemaleSheepUp-RegulationConnexin 43InflammasomesNLR Family, Pyrin Domain-Containing 3 ProteinReceptors, G-Protein-CoupledZearalenonegap junctionGPR30NLRP3 inflammasomeovarian granulosa cellszearalenone

Identifiers

PMID42352304
PMCPMC13297281

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.