How a pheromone wards off pedophilia in mice

Adult male mice tend to be a pretty randy bunch – unchained by humanistic social norms, they freely express their sexuality, often mounting multiple newly introduced females in a day when given the chance. Nevertheless, most adult males seem to have a “legal-or-not” radar, and stay far, far away from prepubescent females.

Why?

Unlike humans who heavily rely on sight and speech, social interactions between mice are influenced by pheromones – chemicals secreted in bodily fluids that act on a special part of a neighbour’s olfactory (smelling) system called the vomeronasal organ (VNO). Pheromones play a huge role in social interactions in mice - they can enhance attraction to a mate, strengthen a female’s memory of her mate’s location, induce abortion of a newly planted embryo and drive maternal aggression. Male mice, for example, secrete a pheromone called ESP1 in their tears that increases a female’s receptivity to his sexual advances. Female mice when housed together prolong each other’s reproductive cycles, thus delaying the onset of the period in which they're willing to mate (aka "in heat" or "estrus").

Since pheromones are so crucial to sexual behaviour in mice, could it be that juvenile females simply lack the “sexy hormone” to attract adult males? Or on the contrary, could it be that the young maidens have a special pheromone to guard them against unwanted advances?

D.M. Ferrero et al. A juvenile mouse pheromone inhibits sexual behaviour through the vomeronasal system. Nature, doi:10.1038/nature12579, 2013.

Researchers used genetic methods to identify numerous protein pheromones in various tissues collected from mice of different ages and sex. One particular putative pheromone –dubbed ESP22- caught their eye.  As you can see below, the gene is highly expressed in tear-producing glands in mice during adolescence (roughly 2-3 weeks of age), but tanked once they came of age. Secreted by acrine cells, ESP22 was also abundant in young mice’s tears, which is a well-known carrier of many types of pheromones.

To establish ESP22 as a functional chemosignal, researchers introduced the protein to neurons in the VNO (pheromone detection system) and used electrodes to monitor if they activated in response– they did! What’s more, by labeling for a protein that is only present shortly AFTER neuronal activation (and thus a sign of recent firing), researchers found that ESP22 also activated neurons in medial amygdala, an almond-shaped area deep in the brain. The medial amygdala is part of the limbic system that receives input from the VNO to heavily influence reproductive and emotional responses in mice.

All these data point to ESP22 as a pheromone involved in sexual behaviour – but WHAT exactly is it doing in teenager mice?

To tease out the answer, researchers simply eliminated the “receiver”: they introduced adolescent females to adult males with a genetic mutation that rendered their VNO pretty much useless. The results were striking: compared to wild-type mice, these males showed vigorous sexual behaviour toward young female mice, making their moves faster (middle graph below, grey-wild type, red-mutant), more frequently (left graph) and spent more time in the act (right graph). This wasn’t because VNO-mutants were hypersexual – when presented with an ADULT female their behaviour was similar to that of wild-type mice.

Grey bar: wild-type adult males, red bar: VNO mutant males. Greys are A LOT friskier than reds

Grey bar: wild-type adult males, red bar: VNO mutant males. Greys are A LOT friskier than reds

These results suggest that ESP22 acts as a deterrent against sexual advances. To further confirm their finding, researchers identified two strains of mice that didn’t express the pheromone during their teenage years. Sure enough, without the suppressor, male mice showed drastically increased sexual behaviour towards these strains (grey bars below, red are normal controls), regardless of the young one's sex. However, when researchers reintroduced the pheromone by painting a synthetic version onto the bodies of ESP22-lacking juvenile mice, the adults once again respectably kept their distance and drastically decreased total mounting attempts.

Finally, when researchers camouflaged oestrus "in heat" ADULT female mice with the pheromone, males approached these willing partners less frequently, and when they did, hesitated for much longer before mounting.

This is a pretty unique finding – generally, pheromones evoke a response from a receiver; here ESP22 actively INHIBITS a behavioural outcome. It’s interesting that the pheromone is present in both sexes – while male-female mounting generally signals reproduction, male-male mounting is more of a struggle for social dominance - hence mounting itself is not inherently always a sexual act. So in a sense (purely speculating) perhaps ESP22 is signalling to societal members “I’m not yet ready for the playing field”, in the context of both sex and power?

Finally, is ESP22 the anti-jailbait for humans too? The answer is a definitive no. Contrary to what commercials tell you, whether pheromones play a role in our social behaviour is still a hotly-debated open question. Humans do not have a functional VNO, hence even if we were to receive pheromone signals, it would have to be through some yet undiscovered mechanism.


Ferrero DM, Moeller LM, Osakada T, Horio N, Li Q, Roy DS, Cichy A, Spehr M, Touhara K, & Liberles SD (2013). A juvenile mouse pheromone inhibits sexual behaviour through the vomeronasal system. Nature PMID: 24089208

 
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