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.