A Heterogeneous Mixture of F-Series Prostaglandins Promotes Sperm Guidance in the Caenorhabditis elegans Reproductive Tract

Hieu D. Hoang, Jeevan K. Prasain, Dixon Dorand, Michael A. Miller

Research output: Contribution to journalArticlepeer-review

44 Scopus citations

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 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.

Original languageEnglish
Article numbere1003271
JournalPLoS genetics
Volume9
Issue number1
DOIs
StatePublished - Jan 2013

Fingerprint

Dive into the research topics of 'A Heterogeneous Mixture of F-Series Prostaglandins Promotes Sperm Guidance in the Caenorhabditis elegans Reproductive Tract'. Together they form a unique fingerprint.

Cite this