ArticleAntioxidants (Basel, Switzerland)2020
Non-Esterified Fatty Acid-Induced Reactive Oxygen Species Mediated Granulosa Cells Apoptosis Is Regulated by Nrf2/p53 Signaling Pathway.
Article in Antioxidants (Basel, Switzerland), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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.
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.
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Who cites it
19 citing papers in PubMed, 19 citations in OpenAlex.
- Lipid dysregulation in mouse ovarian antral follicles after oral exposure to a human relevant mixture of three phthalates.Toxicology · 2026Article
- Comparative effectiveness of propylene glycol-based health programs for controlling ketosis and improving performance in dairy cows.Veterinary world · 2026Article
- NEFA Promotes Bovine Granulosa Cell Apoptosis via Activation of the PERK/eIF2α/ATF4/CHOP Pathway.Veterinary sciences · 2025Article
- NDUFAB1 as a Novel Regulator of NEFA-Induced Metabolic Dysfunction in Bovine Adipocytes.Animals : an open access journal from MDPI · 2025Article
- B-Lymphoid Tyrosine Kinase Crosslinks Redox and Apoptosis Signaling Networks to Promote the Survival of Transplanted Bone Marrow Mesenchymal Stem Cells.Research (Washington, D.C.) · 2025Article
- The role of short-chain fatty acid in metabolic syndrome and its complications: focusing on immunity and inflammation.Frontiers in immunology · 2025Review
- Capsaicin Modulates Hepatic and Intestinal Inflammation and Oxidative Stress by Regulating the Colon Microbiota.Antioxidants (Basel, Switzerland) · 2024Article
- Gut microbial metabolites SCFAs and chronic kidney disease.Journal of translational medicine · 2024Review
- Propolis Ethanolic Extract Attenuates D-gal-induced C2C12 Cell Injury by Modulating Nrf2/HO-1 and p38/p53 Signaling Pathways.International journal of molecular sciences · 2023Article
- Control of Redox Homeostasis by Short-Chain Fatty Acids: Implications for the Prevention and Treatment of Breast Cancer.Pathogens (Basel, Switzerland) · 2023Review
- Transcriptome Analysis Reveals That NEFA and β-Hydroxybutyrate Induce Oxidative Stress and Inflammatory Response in Bovine Mammary Epithelial Cells.Metabolites · 2022Article
- High-Fat Diet and Female Fertility across Lifespan: A Comparative Lesson from Mammal Models.Nutrients · 2022Review
- Non-Esterified Fatty Acid Induces ER Stress-Mediated Apoptosis via ROS/MAPK Signaling Pathway in Bovine Mammary Epithelial Cells.Metabolites · 2022Article
- Article
- Short-Chain Fatty Acids in Chronic Kidney Disease: Focus on Inflammation and Oxidative Stress Regulation.International journal of molecular sciences · 2022Review
- Metabolism of fatty acids in follicular cells, oocytes, and blastocysts.Reproduction & fertility · 2022Review
- Systems biology reveals anatabine to be an NRF2 activator.Frontiers in pharmacology · 2022Article
- Short-chain fatty acids as modulators of redox signaling in health and disease.Redox biology · 2021Review
- Cocultured porcine granulosa cells respond to excess non-esterified fatty acids during in vitro maturation.Journal of ovarian research · 2021Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
Negative energy balance (NEB) during the perinatal period can affect dairy cow follicular development and reduce the fecundity. Non-esterified fatty acid (NEFA) concentration is elevated during NEB, and is known to be toxic for multiple cell types. In the ovary, NEB increased NEFA, and may influences follicular growth and development. However, the effect and mechanism of NEFA on granulosa cells (GCs) in vitro remains unknown. In this study, we found that NEFA dose-dependently induced apoptosis in primary cultured granulosa cells. Mechanistically, our data showed that NEFA significantly increased reactive oxygen species (ROS) levels, resulting in the activation of endoplasmic reticulum stress (ERS) and eventually cell apoptosis in GCs. Moreover, NEFA also increased the phosphorylation levels of ERK1/2 and p38MAPK pathways, upregulated the expression of p53 and potentially promoted its translocation to the nuclear, thus transcriptionally activated Bax, a downstream gene of this pathway. NEFA also promoted nuclear factor E2 (Nrf2) expression and its level in the nuclear. To elucidate the mechanism of NEFA action, N-acetyl-L-cysteine (NAC), a ROS scavenger was used to verify the role of ROS in NEFA induced apoptosis of GCs. NAC pretreatment reversed the NEFA-induced ERS-related protein and apoptosis-related protein levels. Meanwhile, NAC pretreatment also blocked the phosphorylation of ERK1/2 and p38 induced by NEFA, and the nucleation of Nrf2 and p53, suggesting that ROS plays a crucial role in regulating the NEFA-induced apoptosis of GCs. Together, these findings provide an improved understanding of the mechanisms underlying GCs apoptosis, which could potentially be useful for improving ovarian function.
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Registered trials
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 OpenQuestion graph.