A heterogeneous mixture of F-series prostaglandins promotes sperm guidance in the Caenorhabditis elegans reproductive tract

• Published in: PLoS genetics Vol. 9; no. 1; p. e1003271
• Main Authors: Hoang, Hieu D, Prasain, Jeevan K, Dorand, Dixon, Miller, Michael A
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.01.2013; Public Library of Science (PLoS)
• Subjects: Animal reproduction; Animals; Arachidonic Acids - chemistry; Arachidonic Acids - metabolism; Biology; Caenorhabditis elegans; Caenorhabditis elegans - metabolism; Caenorhabditis elegans - physiology; Chromatography; 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; Genetic aspects; Genetics; Genomics; Health aspects; Humans; Male; Mass spectrometry; Mice; Nematodes; Oocytes - metabolism; Oocytes - physiology; Physiological aspects; Prostaglandins; Prostaglandins F - biosynthesis; Prostaglandins F - chemistry; Reproduction - genetics; Reproduction - physiology; Sperm Motility - genetics; Spermatozoa; Spermatozoa - metabolism; Spermatozoa - physiology; United States
• ISSN: 1553-7404; 1553-7390; 1553-7404
• DOI: 10.1371/journal.pgen.1003271

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.