2,5-Hexanedione Affects Ovarian Granulosa Cells in Swine by Regulating the CDKN1A Gene: A Transcriptome Analysis
Open Access
- 7 March 2023
- journal article
- research article
- Published by MDPI AG in Veterinary Sciences
- Vol. 10 (3) , 201
Abstract
N-hexane, a common industrial organic solvent, causes multiple organ damage owing to its metabolite, 2,5-hexanedione (2,5-HD). To identify and evaluate the effects of 2,5-HD on sows’ reproductive performance, we used porcine ovarian granulosa cells (pGCs) as a vehicle and carried out cell morphology and transcriptome analyses. 2,5-HD has the potential to inhibit the proliferation of pGCs and induce morphological changes and apoptosis depending on the dose. RNA-seq analyses identified 4817 differentially expressed genes (DEGs), with 2394 down-regulated and 2423 up-regulated following 2,5-HD exposure treatment. The DEG, cyclin-dependent kinase inhibitor 1A (CDKN1A), according to the Kyoto Encyclopedia of Genes and Genomes enrichment analysis, was significantly enriched in the p53 signaling pathway. Thus, we evaluated its function in pGC apoptosis in vitro. Then, we knocked down the CDKN1A gene in the pGCs to identify its effects on pGCs. Its knockdown decreased pGC apoptosis, with significantly fewer cells in the G1 phase (p < 0.05) and very significantly more cells in the S phase (p < 0.01). Herein, we revealed novel candidate genes that influence pGCs apoptosis and cell cycle and provided new insights into the role of CDKN1A in pGCs during apoptosis and cell cycle arrest.Keywords
Funding Information
- the Cooperative Innovation Project of universities of Anhui Province under Grant (GXXT-2021-055, 202103a06020013)
- the Major special science and technology project of Anhui Province under Grant (GXXT-2021-055, 202103a06020013)
This publication has 68 references indexed in Scilit:
- Genetic Polymorphisms and Protein Expression of NRF2 and Sulfiredoxin Predict Survival Outcomes in Breast CancerCancer Research, 2012
- A GREM1 Gene Variant Associates with Diabetic NephropathyJournal of the American Society of Nephrology, 2010
- Chloroquine activates the p53 pathway and induces apoptosis in human glioma cellsNeuro-Oncology, 2010
- ANKRD1, the Gene Encoding Cardiac Ankyrin Repeat Protein, Is a Novel Dilated Cardiomyopathy GeneJACC, 2009
- Probing Mechanisms of Axonopathy. Part II: Protein Targets of 2,5-Hexanedione, the Neurotoxic Metabolite of the Aliphatic Solvent n-HexaneToxicological Sciences, 2008
- Spermatid Head Retention as a Marker of 2,5-Hexanedione-induced Testicular Toxicity in the RatToxicologic Pathology, 2008
- Apoptotic and necrotic effects of hexanedione derivatives on the human neuroblastoma line SK-N-SHToxicology, 2007
- Transcriptional regulation of the cyclin-dependent kinase inhibitor 1A (p21) gene by NFI in proliferating human cellsNucleic Acids Research, 2006
- 2,5-Hexanedione-Induced Testicular InjuryAnnual Review of Pharmacology and Toxicology, 2003
- Localized calcium signalling and neuronal integration in cerebellar Purkinje neuronesCell Calcium, 1996