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 PGF2α 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.
Highlights
The union of oocyte and sperm, known as fertilization, is paramount to the survival of animal species [1,2,3,4]
Prostaglandins are widespread signaling molecules derived from polyunsaturated fatty acids or PUFAs
We show that C. elegans oocytes synthesize a heterogenous mixture of structurally related F-series prostaglandins derived from different PUFA classes, including the enantiomer of PGF2a
Summary
The union of oocyte and sperm, known as fertilization, is paramount to the survival of animal species [1,2,3,4]. On the other hand, are smaller mobile cells capable of sensing their environment and responding with changes in motility. Sperm have a relatively simple job—find an oocyte and provide it with a second set of chromosomes. While much has been learned about sperm motility in aquatic species [5,6], the mechanisms that guide sperm to oocytes in internally fertilizing animals are less well understood. Evidence is emerging that lipid signaling molecules, such as steroids and prostaglandins are important regulators of sperm motility in the human female reproductive tract [9,10,11,12,13]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
