Stress response pathways protect germ cells from omega-6 polyunsaturated fatty acid-mediated toxicity in Caenorhabditis elegans.

Abstract

Polyunsaturated fatty acids serve both structural and functional roles as membrane components and precursors for a number of different factors involved in inflammation and signaling. These fatty acids are required in the human diet, although excess dietary intake of omega-6 fatty polyunsaturated fatty acids may have a negative influence on human health. In the model nematode, Caenorhabditis elegans, dietary exposure to dihomo-gamma-linolenic acid (DGLA), an omega-6 fatty acid, causes the destruction of germ cells and leads to sterility. In this study we used genetic and microscopic approaches to further characterize this phenomenon. We found that strains carrying mutations in genes involved in lipid homeostasis enhanced sterility phenotypes, while mutations reducing the activity of the conserved insulin/IGF signaling pathway suppressed sterility phenotypes. Exposure to a mild heat stress prior to omega-6 fatty acid treatment led to an adaptive or hormetic response, resulting in less sterility. Mutations in skn-1 and knockdown of genes encoding phase II detoxification enzymes led to increased sterility in the presence of dietary DGLA. Thus, detoxification systems and genetic changes that increase overall stress responses protect the germ cells from destruction. Microscopic analyses revealed that dietary DGLA leads to deterioration of germ cell membranes in the proliferative and transition zones of the developing germ line. Together, these data demonstrate that specific omega-6 polyunsaturated fatty acids, or molecules derived from them, are transported to the germ line where they disrupt the rapidly expanding germ cell membranes, leading to germ cell death.

• Authors: Christopher M Webster, Marshall L Deline, Jennifer L Watts
• Journal: Developmental biology (Dev Biol) Vol. 373 Issue 1 Pg. 14-25 (Jan 01 2013) ISSN: 1095-564X [Electronic] United States
• PMID: 23064027 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2012 Elsevier Inc. All rights reserved.

Chemical References

• Caenorhabditis elegans Proteins
• DNA-Binding Proteins
• Dietary Fats
• Indoles
• Insulin
• Transcription Factors
• skn-1 protein, C elegans
• DAPI
• 8,11,14-Eicosatrienoic Acid

Topics

• 8,11,14-Eicosatrienoic Acid (toxicity)
• Animals
• Caenorhabditis elegans
• Caenorhabditis elegans Proteins (genetics)
• Cell Death (drug effects)
• Cell Membrane (drug effects)
• Chromatography, Gas
• DNA-Binding Proteins (genetics)
• Dietary Fats (toxicity)
• Germ Cells (drug effects, physiology)
• Hot Temperature
• Indoles
• Infertility (etiology)
• Insulin (metabolism)
• Microscopy, Fluorescence
• Mutation (genetics)
• RNA Interference
• Real-Time Polymerase Chain Reaction
• Signal Transduction (genetics)
• Species Specificity
• Stress, Physiological (physiology)
• Transcription Factors (genetics)