| 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
|
|
WOS Category
|
DEVELOPMENTAL BIOLOGY
CELL BIOLOGY
|
| Resource |
| C.elegans |
tm3294 |
