@article{08dac0439bf6466ea4502f17666af176,
title = "Insulin/FOXO Signaling Regulates Ovarian Prostaglandins Critical for Reproduction",
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.",
author = "Edmonds, \{Johnathan W.\} and Prasain, \{Jeevan K.\} and Dixon Dorand and Youfeng Yang and Hoang, \{Hieu D.\} and Jack Vibbert and Kubagawa, \{Homare M.\} and Miller, \{Michael A.\}",
note = "Funding Information: We thank S. Barnes and R. Moore for helpful discussions and technical support, G. Seydoux for the pie-1 expression plasmid, and the UAB Targeted Metabolomics and Proteomics Laboratory, which has been supported in part by the UAB Comprehensive Cancer (P30CA13148), the UAB Center for Nutrient-Gene Interaction (U54 CA100949), the Purdue-UAB Botanical Center for Age-Related Disease (P50 AT00477), the UAB O'Brien Acute Kidney Injury Center (P30 DK079337), the UAB Skin Disease Research Center (P30 AR50948), and the UAB Lung Health Center. We also thank S. Barnes, H. Bellen, T. Benveniste, P. Cottee, S.M. Han, T. Mahoney, and B. Yoder for comments on the manuscript. Some strains were provided by the Caenorhabditis Genetics Center, which is funded by the NIH. The gst-4 mutant strains were created by the C. elegans Gene Knockout Consortium, which is funded by the NIH, and the Japanese National Bioresource Project, which is supported by the Ministry of Education, Culture, Science, Sports and Technology. This work was supported by the NIH (R01GM085105 to M.A.M., including an ARRA administrative supplement). ",
year = "2010",
month = dec,
day = "14",
doi = "10.1016/j.devcel.2010.11.005",
language = "English",
volume = "19",
pages = "858--871",
journal = "Developmental cell",
issn = "1534-5807",
number = "6",
}