Cyclohexyl acetate functions like a volatile sex pheromone mimic in Caenorhabditis nematodes

TL;DR

This study shows that cyclohexyl acetate mimics a male-specific attractant in nematodes, using a different sensory pathway than natural pheromones.

Contribution

The study identifies cyclohexyl acetate as a volatile compound that mimics sex pheromone effects in Caenorhabditis nematodes through a novel sensory pathway.

Findings

Cyclohexyl acetate acts as a male-specific attractant in Caenorhabditis nematodes.

Cyclohexyl acetate perception involves AWCon neurons and srd-1-independent pathways.

Cyclohexyl acetate is a structural analog, not a major component of natural volatile sex pheromones.

Abstract

Nematodes communicate via diverse sex pheromones, including long-range volatile signals, short-range chemical cues, and contact-dependent molecules. While the ascaroside family of small molecules that mediate short-range attraction is well characterized, the identities and roles of volatile sex pheromones (VSPs) that act over longer ranges remain unknown.

Using GC–MS analysis of crude VSP extracts, we identified cyclohexyl acetate (CA) as a candidate mimic, sharing retention time and mass spectral features with natural VSPs. Behavioral assays demonstrated that CA acts as a concentration-dependent, male-specific attractant in Caenorhabditis. Pre-exposure to VSPs induced cross-adaptation to CA, suggesting shared sensory processing. Surprisingly, genetic and calcium imaging analyses revealed that CA perception is mediated primarily by AWCon (str-2-expressing) neurons and involves VSP chemoreceptor srd-1-independent pathways, which are distinct from the neural pathways involved in natural VSP perception.

These data indicate that CA is unlikely to be a major VSP constituent; rather, it is a structural analog that elicits male-specific attraction via a parallel sensory circuit. The endogenous source of CA in C. remanei remains unresolved; our data do not establish whether females produce CA. Its structural and behavioral mimicry provides new insights into the complexity of chemosensory signaling and the potential for interspecies chemical eavesdropping in nematode ecology.

The online version contains supplementary material available at 10.1186/s12915-026-02510-0.

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