Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

Oocyte signals derived from polyunsaturated fatty acids control sperm recruitment in vivo

Abstract

A fundamental question in animal development is how motile cells find their correct target destinations. During mating in the nematode Caenorhabditis elegans, males inject sperm through the hermaphrodite vulva into the uterus. Amoeboid sperm crawl around fertilized eggs to the spermatheca – a convoluted tube where fertilization occurs1,2. Here, we show that polyunsaturated fatty acids (PUFAs), the precursors of eicosanoid signalling molecules, function in oocytes to control directional sperm motility within the uterus. PUFAs are transported from the intestine, the site of fat metabolism, to the oocytes yolk, which is a lipoprotein complex. Loss of the RME-2 low-density lipoprotein (LDL) receptor, which mediates yolk endocytosis3 and fatty acid transport into oocytes, causes severe defects in sperm targeting. We used an RNAi screen to identify lipid regulators required for directional sperm motility. Our results support the hypothesis that PUFAs function in oocytes as precursors of signals that control sperm recruitment to the spermatheca. A common property of PUFAs in mammals and C. elegans is that these fats control local recruitment of motile cells to their target tissues.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Sperm migration in the hermaphrodite reproductive tract.
Figure 2: Fatty acid transport and yolk analysis.

Similar content being viewed by others

References

  1. Singson, A. Every sperm is sacred: fertilization in Caenorhabditis elegans. Dev. Biol. 230, 101–109 (2001).

    Article  CAS  Google Scholar 

  2. Ward, S. & Carrel, J. S. Fertilization and sperm competition in the nematode Caenorhabditis elegans. Dev. Biol. 73, 304–321 (1979).

    Article  CAS  Google Scholar 

  3. Grant, B. & Hirsh, D. Receptor-mediated endocytosis in the Caenorhabditis elegans oocyte. Mol. Biol. Cell 10, 4311–4326 (1999).

    Article  CAS  Google Scholar 

  4. Kosinski, M., McDonald, K., Schwartz, J., Yamamoto, I. & Greenstein, D. C. elegans sperm bud vesicles to deliver a meiotic maturation signal to distant oocytes. Development 132, 3357–3369 (2005).

    Article  CAS  Google Scholar 

  5. Hill, K. L. & L'Hernault, S. W. Analyses of reproductive interactions that occur after heterospecific matings within the genus Caenorhabditis. Dev. Biol. 232, 105–114 (2001).

    Article  CAS  Google Scholar 

  6. Vacquier, V. D. Evolution of gamete recognition proteins. Science 281, 1995–1998 (1998).

    Article  CAS  Google Scholar 

  7. Beanan, M. J. & Strome, S. Characterization of a germ-line proliferation mutation in C. elegans. Development 116, 755–766 (1992).

    CAS  PubMed  Google Scholar 

  8. Barton, M. K., Schedl, T. B. & Kimble, J. Gain-of-function mutations of fem-3, a sex-determination gene in Caenorhabditis elegans. Genetics 115, 107–119 (1987).

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Graham, P. L., Schedl, T. & Kimble, J. More mog genes that influence the switch from spermatogenesis to oogenesis in the hermaphrodite germ line of Caenorhabditis elegans. Dev. Genet. 14, 471–484 (1993).

    Article  CAS  Google Scholar 

  10. Francis, R., Barton, M. K., Kimble, J. & Schedl, T. gld-1, a tumor suppressor gene required for oocyte development in Caenorhabditis elegans. Genetics 139, 579–606 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Kurzchalia, T. V. & Ward, S. Why do worms need cholesterol? Nature Cell Biol. 5, 684–688 (2003).

    Article  CAS  Google Scholar 

  12. Watts, J. L. & Browse, J. Genetic dissection of polyunsaturated fatty acid synthesis in Caenorhabditis elegans. Proc. Natl Acad. Sci. USA 99, 5854–5859 (2002).

    Article  CAS  Google Scholar 

  13. Watts, J. L., Phillips, E., Griffing, K. R. & Browse, J. Deficiencies in C20 polyunsaturated fatty acids cause behavioral and developmental defects in Caenorhabditis elegans fat-3 mutants. Genetics 163, 581–589 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  14. McKay, R. M., McKay, J. P., Avery, L. & Graff, J. M. C elegans: a model for exploring the genetics of fat storage. Dev. Cell 4, 131–142 (2003).

    Article  CAS  Google Scholar 

  15. Funk, C. D. Prostaglandins and leukotrienes: advances in eicosanoid biology. Science 294, 1871–1875 (2001).

    Article  CAS  Google Scholar 

  16. Kahn-Kirby, A. H. et al. Specific polyunsaturated fatty acids drive TRPV-dependent sensory signaling in vivo. Cell 119, 889–900 (2004).

    Article  CAS  Google Scholar 

  17. Reinke, V., Gil, I. S., Ward, S. & Kazmer, K. Genome-wide germline-enriched and sex-biased expression profiles in Caenorhabditis elegans. Development 131, 311–323 (2004).

    Article  CAS  Google Scholar 

  18. Kohara, Y. Systematic analysis of gene expression of the C. elegans genome. Tanpakushitsu Kakusan Koso 46, 2425–2431 (2001).

    CAS  PubMed  Google Scholar 

  19. Sijen, T. et al. On the role of RNA amplification in dsRNA-triggered gene silencing. Cell 107, 465–476 (2001).

    Article  CAS  Google Scholar 

  20. Sharrock, W. J., Sutherlin, M. E., Leske, K., Cheng, T. K. & Kim, T. Y. Two distinct yolk lipoprotein complexes from Caenorhabditis elegans. J. Biol. Chem. 265, 14422–14431 (1990).

    CAS  PubMed  Google Scholar 

  21. Hall, D. H. et al. Ultrastructural features of the adult hermaphrodite gonad of Caenorhabditis elegans: relations between the germ line and soma. Dev. Biol. 212, 101–123 (1999).

    Article  CAS  Google Scholar 

  22. Janssen-Timmen, U., Tomic, I., Specht, E., Beilecke, U. & Habenicht, A. J. The arachidonic acid cascade, eicosanoids, and signal transduction. Ann. NY Acad. Sci. 733, 325–334 (1994).

    Article  CAS  Google Scholar 

  23. Luster, A. D. & Tager, A. M. T-cell trafficking in asthma: lipid mediators grease the way. Nature Rev. Immunol. 4, 711–724 (2004).

    Article  CAS  Google Scholar 

  24. Tager, A. M. et al. Leukotriene B4 receptor BLT1 mediates early effector T cell recruitment. Nature Immunol. 4, 982–990 (2003).

    Article  CAS  Google Scholar 

  25. Goodarzi, K., Goodarzi, M., Tager, A. M., Luster, A. D. & von Andrian, U. H. Leukotriene B4 and BLT1 control cytotoxic effector T cell recruitment to inflamed tissues. Nature Immunol. 4, 965–973 (2003).

    Article  CAS  Google Scholar 

  26. Eisenbach, M. & Giojalas, L. C. Sperm guidance in mammals – an unpaved road to the egg. Nature Rev. Mol. Cell Biol. 7, 276–285 (2006).

    Article  CAS  Google Scholar 

  27. Timmons, L. & Fire, A. Specific interference by ingested dsRNA. Nature 395, 854 (1998).

    Article  CAS  Google Scholar 

  28. Merris, M. et al. Sterol effects and sites of sterol accumulation in Caenorhabditis elegans: developmental requirement for 4α-methyl sterols. J. Lipid Res. 44, 172–181 (2003).

    Article  CAS  Google Scholar 

  29. Miller, M. A. et al. A sperm cytoskeletal protein that signals oocyte meiotic maturation and ovulation. Science 291, 2144–2147 (2001).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank D. Greenstein, G. Marques and R. Steele for comments on the manuscript. Some strains were provided by the Caenorhabditis Genetics Center, which is funded by the National Institutes of Health (NIH). Financial support came from the University of Alabama at Birmingham (UAB), Department of Cell Biology, including Howard Hughes Medical Institute (HMMI) start-up funds delegated by UAB, UAB Comprehensive Cancer Center Junior Faculty Development and American Cancer Society Institutional Research (ACSIRG) grants to M.A.M., and an NIH grant (RO1DK074114) to J.L.W.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Michael A. Miller.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kubagawa, H., Watts, J., Corrigan, C. et al. Oocyte signals derived from polyunsaturated fatty acids control sperm recruitment in vivo. Nat Cell Biol 8, 1143–1148 (2006). https://doi.org/10.1038/ncb1476

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ncb1476

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing