Mechanisms of TGFß in prostaglandin synthesis and sperm guidance in Caenorhabditis elegans

Dev Dyn. 2021 Jul;250(7):932-942. doi: 10.1002/dvdy.296. Epub 2021 Jan 23.

Abstract

Background: The transparent epidermis of Caenorhabditis elegans makes it an attractive model to study sperm motility and migration within an intact reproductive tract. C elegans synthesize specific F-series prostaglandins (PGFs) that are important for guiding sperm toward the spermatheca. These PGFs are synthesized from polyunsaturated fatty acid (PUFA) precursors, such as arachidonic acid (AA), via a novel pathway, independent of the classical cyclooxygenases (Cox) responsible for most PG synthesis. While the enzyme(s) responsible for PG synthesis has yet to be identified, the DAF-7 TGFß pathway has been implicated in modulating PG levels and sperm guidance.

Results: We find that the reduced PGF levels in daf-1 type I receptor mutants are responsible for the sperm guidance defect. The lower level of PGs in daf-1 mutants is due in part to the inaccessibility of AA. Finally, lipid analysis and assessment of sperm guidance in daf-1;daf-3 double mutants suggest DAF-3 suppresses PG production and sperm accumulation at the spermatheca. Our data suggest that DAF-3 functions in the nervous system, and possibly the germline, to affect sperm guidance.

Conclusion: The C elegans TGFß pathway regulates many pathways to modulate PG metabolism and sperm guidance. These pathways likely function in the nervous system and possibly the germline.

Keywords: Caenorhabditis elegans; daf-1; daf-3; daf-7; oocyte; sperm.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Caenorhabditis elegans
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism
  • Female
  • Male
  • Prostaglandins / biosynthesis*
  • Signal Transduction / drug effects
  • Signal Transduction / genetics
  • Sperm Motility / drug effects
  • Sperm Motility / genetics*
  • Spermatozoa / drug effects
  • Spermatozoa / metabolism
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / metabolism
  • Transforming Growth Factor beta / pharmacology
  • Transforming Growth Factor beta / physiology*

Substances

  • Caenorhabditis elegans Proteins
  • DAF-7 protein, C elegans
  • Prostaglandins
  • Transforming Growth Factor beta