title: A heterogeneous mixture of F-series prostaglandins promotes sperm guidance in the Caenorhabditis elegans reproductive tract.
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.
authors: Department of Cell Biology, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
authors: Hieu D
authors: HD
authors: Hoang
authors: Jeevan K
authors: JK
authors: Prasain
authors: Dixon
authors: D
authors: Dorand
authors: Michael A
authors: MA
authors: Miller
mesh_terms: D000818:Animals; D001095:Arachidonic Acids / Q000737:chemistry / Q000378:metabolism; D017173:Caenorhabditis elegans / Q000378:metabolism / Q000502:physiology; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism; D015525:Fatty Acids, Omega-3 / Q000737:chemistry / Q000378:metabolism; D043371:Fatty Acids, Omega-6 / Q000737:chemistry / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D009865:Oocytes / Q000378:metabolism / Q000502:physiology; D011460:Prostaglandins F / Q000096:biosynthesis / Q000737:chemistry; D012098:Reproduction / Q000235:genetics / Q000502:physiology; D013081:Sperm Motility / Q000235:genetics; D013094:Spermatozoa / Q000378:metabolism / Q000502:physiology
chemical_list: D001095:Arachidonic Acids; D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6; D011460:Prostaglandins F; D003577:Cytochrome P-450 Enzyme System
references: Development. 1992 Nov;116(3):755-66
references: 1289064
references: Methods. 2003 Aug;30(4):313-21
references: 12828945
references: Dev Biol. 2001 Apr 1;232(1):105-14
references: 11254351
references: Nutr Rev. 1973 Aug;31(8):248-9
references: 4586201
references: Nat Cell Biol. 2002 Oct;4 Suppl:s57-63
references: 12479616
references: Adv Exp Med Biol. 2011;713:65-80
references: 21432014
references: PLoS One. 2009 Dec 08;4(12):e8211
references: 19997608
references: Mol Cell Endocrinol. 2009 Jul 10;306(1-2):59-65
references: 19481685
references: Drug Metab Rev. 2007;39(2-3):515-38
references: 17786636
references: Annu Rev Physiol. 2012;74:453-75
references: 22017176
references: Am J Hum Genet. 2004 May;74(5):817-26
references: 15042513
references: Mol Pharmacol. 2012 Oct;82(4):679-86
references: 22772592
references: Nature. 1998 Oct 29;395(6705):854
references: 9804418
references: Anal Biochem. 2005 Nov 1;346(1):1-42
references: 15961057
references: Nature. 2011 Mar 17;471(7338):387-91
references: 21412339
references: J Biol Chem. 1964 Nov;239:PC4006-8
references: 14257636
references: Annu Rev Pharmacol Toxicol. 1998;38:97-120
references: 9597150
references: Adv Exp Med Biol. 2013;757:321-50
references: 22872482
references: J Biol Chem. 2008 Jun 6;283(23):15533-7
references: 18285331
references: Biol Reprod. 2007 Aug;77(2):190-201
references: 17442851
references: Adv Exp Med Biol. 2013;757:277-320
references: 22872481
references: Annu Rev Physiol. 2008;70:93-117
references: 17988206
references: Dev Biol. 2007 Jan 15;301(2):432-46
references: 16982048
references: Fertil Steril. 1988 Feb;49(2):322-7
references: 3338588
references: Science. 2001 Nov 30;294(5548):1871-5
references: 11729303
references: J Biol Chem. 1967 Nov 25;242(22):5336-43
references: 6070851
references: Nature. 2011 Mar 17;471(7338):382-6
references: 21412338
references: Proc Natl Acad Sci U S A. 2002 Apr 30;99(9):5854-9
references: 11972048
references: Curr Biol. 2006 Feb 7;16(3):252-63
references: 16461278
references: Endocrinology. 1981 Feb;108(2):457-63
references: 7449734
references: J Biol Chem. 2007 Jan 5;282(1):329-36
references: 17107953
references: EMBO J. 2012 Apr 4;31(7):1654-65
references: 22354039
references: Trends Endocrinol Metab. 2009 Mar;20(2):58-65
references: 19181539
references: J Lipid Res. 2008 Apr;49(4):893-902
references: 18187404
references: Biochem Soc Trans. 2010 Oct;38(5):1270-4
references: 20863297
references: Rapid Commun Mass Spectrom. 2006;20(20):3023-9
references: 16986207
references: J Reprod Fertil. 1985 Jan;73(1):139-46
references: 3855460
references: J Vis Exp. 2012 Jun 10;(64):e4019
references: 22710399
references: Dev Biol. 1979 Dec;73(2):304-21
references: 499670
references: J Cell Biol. 2012 Aug 20;198(4):731-48
references: 22908315
references: Anal Biochem. 2005 Aug 15;343(2):203-11
references: 16004953
references: Dev Biol. 2011 Nov 1;359(1):47-58
references: 21889935
references: Biol Reprod. 2010 Oct;83(4):507-13
references: 20463353
references: Nature. 2001 Oct 11;413(6856):603-9
references: 11595941
references: Cell. 2004 Dec 17;119(6):889-900
references: 15607983
references: Proc Natl Acad Sci U S A. 2001 Oct 23;98(22):12527-31
references: 11675491
references: Nat Rev Mol Cell Biol. 2006 Apr;7(4):276-85
references: 16607290
references: Prostaglandins Other Lipid Mediat. 2002 Aug;68-69:401-7
references: 12432932
references: Dev Biol. 1999 Jan 1;205(1):111-28
references: 9882501
references: Biochem Biophys Res Commun. 2000 May 27;272(1):263-9
references: 10872837
references: Nat Cell Biol. 2006 Oct;8(10):1143-8
references: 16998478
references: Arch Biochem Biophys. 2008 Apr 1;472(1):65-75
references: 18282462
references: Free Radic Biol Med. 1997;23(6):943-54
references: 9378374
references: Dev Cell. 2010 Dec 14;19(6):858-71
references: 21145501
references: Mech Dev. 2009 May-Jun;126(5-6):382-93
references: 19368796
references: Mol Biol Cell. 1999 Dec;10(12):4311-26
references: 10588660
references: Dev Dyn. 2010 May;239(5):1265-81
references: 20034089