RRC ID 46587
Author Edmonds JW, Prasain JK, Dorand D, Yang Y, Hoang HD, Vibbert J, Kubagawa HM, Miller MA.
Title Insulin/FOXO signaling regulates ovarian prostaglandins critical for reproduction.
Journal Dev Cell
Abstract Abnormalities in insulin/IGF-1 signaling are associated with infertility, but the molecular mechanisms are not well understood. Here we use liquid chromatography with electrospray ionization tandem mass spectrometry to show that the C. elegans insulin/FOXO pathway regulates the metabolism of locally acting lipid hormones called prostaglandins. C. elegans prostaglandins are synthesized without prostaglandin G/H synthase homologs, the targets of nonsteroidal anti-inflammatory drugs. Our results support the model that insulin signaling promotes the conversion of oocyte polyunsaturated fatty acids (PUFAs) into F-series prostaglandins that guide sperm to the fertilization site. Reduction in insulin signaling activates DAF-16/FOXO, which represses the transcription of germline and intestinal genes required to deliver PUFAs to oocytes in lipoprotein complexes. Nutritional and neuroendocrine cues target this mechanism to control prostaglandin metabolism and reproductive output. Prostaglandins may be conserved sperm guidance factors and widespread downstream effectors of insulin actions that influence both reproductive and nonreproductive processes.
Volume 19(6)
Pages 858-71
Published 2010-12-14
DOI 10.1016/j.devcel.2010.11.005
PII S1534-5807(10)00532-0
PMID 21145501
PMC PMC3026445
MeSH Animals Animals, Genetically Modified Base Sequence Caenorhabditis elegans / genetics Caenorhabditis elegans / physiology* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / physiology* DNA Primers / genetics Fatty Acids, Unsaturated / metabolism Female Forkhead Transcription Factors / physiology* Genes, Helminth Insulin / physiology* Male Models, Biological Mutation Oocytes / physiology Ovary / physiology* Prostaglandins F / physiology* Receptor, Insulin / genetics Receptor, Insulin / physiology Reproduction / physiology Signal Transduction Spectrometry, Mass, Electrospray Ionization Sperm Motility / physiology Tandem Mass Spectrometry Transcription Factors / physiology
IF 10.092
Times Cited 45
C.elegans tm3294