RRC ID 46355
Author Hoang HD, Prasain JK, Dorand D, Miller MA.
Title A heterogeneous mixture of F-series prostaglandins promotes sperm guidance in the Caenorhabditis elegans reproductive tract.
Journal PLoS Genet
Abstract The mechanisms that guide motile sperm through the female reproductive tract to oocytes are not well understood. We have shown that Caenorhabditis elegans oocytes synthesize sperm guiding F-series prostaglandins from polyunsaturated fatty acid (PUFA) precursors provided in yolk lipoprotein complexes. Here we use genetics and electrospray ionization tandem mass spectrometry to partially delineate F-series prostaglandin metabolism pathways. We show that omega-6 and omega-3 PUFAs, including arachidonic and eicosapentaenoic acids, are converted into more than 10 structurally related F-series prostaglandins, which function collectively and largely redundantly to promote sperm guidance. Disruption of omega-3 PUFA synthesis triggers compensatory up-regulation of prostaglandins derived from omega-6 PUFAs. C. elegans F-series prostaglandin synthesis involves biochemical mechanisms distinct from those in mammalian cyclooxygenase-dependent pathways, yet PGF(2α) stereoisomers are still synthesized. A comparison of F-series prostaglandins in C. elegans and mouse tissues reveals shared features. Finally, we show that a conserved cytochrome P450 enzyme, whose human homolog is implicated in Bietti's Crystalline Dystrophy, negatively regulates prostaglandin synthesis. These results support the model that multiple cyclooxygenase-independent prostaglandins function together to promote sperm motility important for fertilization. This cyclooxygenase-independent pathway for F-series synthesis may be conserved.
Volume 9(1)
Pages e1003271
Published 2013-1-1
DOI 10.1371/journal.pgen.1003271
PMID 23382703
PMC PMC3561059
MeSH Animals Arachidonic Acids / chemistry Arachidonic Acids / metabolism Caenorhabditis elegans* / metabolism Caenorhabditis elegans* / physiology Cytochrome P-450 Enzyme System / genetics Cytochrome P-450 Enzyme System / metabolism Fatty Acids, Omega-3 / chemistry Fatty Acids, Omega-3 / metabolism Fatty Acids, Omega-6 / chemistry Fatty Acids, Omega-6 / metabolism Female Humans Male Mice Oocytes* / metabolism Oocytes* / physiology Prostaglandins F* / biosynthesis Prostaglandins F* / chemistry Reproduction* / genetics Reproduction* / physiology Sperm Motility / genetics Spermatozoa* / metabolism Spermatozoa* / physiology
IF 5.175
Times Cited 33
C.elegans tm2711 tm3224