Sexuality Is in the Roof of the Mouth, Not in the Brain!

For years, researchers intensely sought for the Holly Grail of sexuality: what makes a man behave like a man and a woman like a woman (or if you want, a gay like a woman and a lesbian like a man). They have sliced the brain in all the possible variants and �no striking results. No dramatic differences between male and female brains. And now a new research at Harvard University comes to mock all these efforts: it was not in the brain at all where the difference had to be sought for and found.

It appears that the epicenter of sex-specific behavior in most vertebrates is a small sensory organ encountered in the roof of the mouth of all terrestrial vertebrates except monkeys, apes and humans.

The new research shows that the impairment in the function of the Jacobson's or vomeronasal organ induces male behavior in female mice, like mounting and pelvic thrusting while losing female behaviors like nesting and nursing. "These results are flabbergasting. Nobody had imagined that a simple mutation like this could induce females to behave so thoroughly like males.", said Catherine Dulac, Higgins Professor of Molecular and Cellular Biology in Harvard's Faculty of Arts and Sciences.

Even if humans lack a vomeronasal organ, this give clues for research into sex-specific human behavior. In most mammals, the flehmen behavior is well known and quite frezuent. That's when males sniff with the roof of their mouth the female's genitalia: the Jacobson's organ detects pheromones and hormonal cargo from urine, indicating to the male if the female is fertile, and thus available (as in most mammals, only in that moment females mate).

The research team investigated female mice mutant in TRPC2, an ion channel whose absence leaves non-functional the vomeronasal organ. They found that these females - when kept in a cage with mature sexually experienced males - started a typically male courtship activity: harassing their cagemates, sniffing the males' hindquarters, and emitting complex ultrasonic calls that are part of the male mouse's courtship ritual. The female mutants would finish their repertoire of male sexual behavior by mounting and thrusting the unfortunate males.

The males counteracted with increased aggression toward the mutant females, eventually mating with all of them. After giving birth, the females displayed an astonishing lack of maternal behavior. Normal female mice spend about 80 % of their time in their nest caring the offspring, but the mutant females started to wander away two days after giving birth, eventually leaving the nest altogether.

While lactating, female mice will normally be extremely aggressive towards males and reject their advances, but the mutant females were highly receptive to sexual encounters.

"There are two possible interpretations. Either the vomeronasal organ may be needed to grow a female-specific neural circuit during development, or the mature female mouse brain may require vomeronasal activity to repress male behavior." said Dulac.

To check these two possibilities, the team excised the vomeronasal organs in normal adult females. These females started to adopt the male behavior, despite the fact that they had sex hormone levels and estrus cycles indistinguishable from those of normal females, just like mutant females had.

"It had previously been thought that entirely different neural circuits, modulated by these hormones, controlled sex-specific behavior. Remarkably, our work suggests that neuronal circuits underlying male-specific behaviors develop and persist in the female mouse brain, but are repressed by the normal activity of the vomeronasal organ." said Dulac.

"In fact, our research suggests a new model where exactly the same neural circuitry exists in males and females. In this model, only the vomeronasal pathway itself -- which serves as a switch that represses male behavior while promoting female behavior -- is dimorphic. While male and female bodies are strikingly different physiologically, it appears the same cannot be said for the brain." said Dulac.

The team is now investigating the sexual behavior of male mice mutants for TRPC2 to see if they have female-like displays.