Sex does strange things to males. Specifically, to some kinds of male mice. When a male mouse is a virgin, he makes for a terrible father figure. Male mice who haven’t mated show a lot of aggression toward baby mice (pups) and will attack and kill them if you let them.

But what happens when you give that male mouse a lovely little mate? After mating and a couple of weeks with a female, the male mice that formerly would have attacked and killed pups on sight are completely different. They start displaying nurturing behavior, hovering over the pups and generally becoming devoted dads.

But the pups aren’t any different. The small and sight of them is the same. It’s the same stimulus, but for the male, it’s an entirely different response. What is changing? What is turning these destructive dudes into devoted dads?

Tachikawa et al. “Behavioral Transition fromAttack to Parenting in Male Mice: A Crucial Role of the Vomeronasal System” Journal of Neuroscience, 2013.
(Source)

What is changing these mice into dads? Well, the one big difference here is contact with a female, not exposure to the pups. What does a female mouse have that might change a male mouse’s mind? Pheromones. While pheromones among humans are theoretical at best (and most often the source of awesome jokes like “Sex Panther: 60{9f43b4361d9a125bc126dd2a2d1949be02545ec69880430bc4fed2272fd72da3} of the time, it works every time”), pheromones in many other animals carry very important signals.

Pheromones aren’t scents, exactly. At least, they aren’t detected like most scents are through the olfactory bulbs. Instead, they are detected through the vomeronasal organ (VNO), which is part of the accessory, rather than the primary, olfactory system. While signals from the VNO will go to olfactory processing, they also disperse widely around the brain, including to areas like the hypothalamus and amygdala, where they can change an animal’s behavior.

The authors of this paper wanted to find out what role the VNO played (and thus, the role that pheromones play) in the change from an aggressive male to a fatherly one.

First, they looked at how the mice in their behavioral facility acted toward pups. When the male mice were virgins, 81{9f43b4361d9a125bc126dd2a2d1949be02545ec69880430bc4fed2272fd72da3} of them displayed aggression toward all pups. But when you put them with a female, the aggressive behavior gradually began to decrease.

You can see above measures of male mouse behavior when exposed to pups, before and over time after mating with a female, where the darkest shades represent the most aggressive behaviors, and the light shades represent the most parental behaviors. Over time, as the males lived with females, their aggression gradually decreased, until by the time the female gave birth, they showed full parenting behavior and no aggression toward pups. It took significant time, at least 11 days to see a significant decrease, but by the end, 88{9f43b4361d9a125bc126dd2a2d1949be02545ec69880430bc4fed2272fd72da3} of the new fathers showed good parenting behavior.
(Measures of parents behavior score. New mouse dads score 100{9f43b4361d9a125bc126dd2a2d1949be02545ec69880430bc4fed2272fd72da3}!)

And it’s not just their OWN pups, like you might expect. When the scientists lowered a wire mesh ball with three pups in it into the cage (gotta have a barrier there…just in case), the new fathers sniffed, licked, and then began to build a nest. But when virgin males saw the mesh ball, they eyed it nastily, and ended up trying to bite it. Different styles, indeed.

But after the male mice were exposed to the pups, both the virgins and the fathers were looked at for c-Fos expression. c-Fos is one of the immediate early genes that control the expression of many other genes. In the brain, you can use the amount of c-Fos present after a stimulus (like, say, pups in a ball) to determine what areas of the brain increased activity due to the stimulus.

In this case, the authors looked at the pathways associated with the VNO. They found significant c-Fos increases in places like the accessory olfactory bulb (a stopover station for VNO signals), and several areas of the hypothalamus, including the medial preoptic nucleus and medial preoptic area (yes, different things), both of which are associated with copulation and aggression. They also saw c-Fos activation in the ventromedial hypothalamic nucleus.

All this is well and good, but it’s the differences that matter. While virgin males had high c-Fos activation in all areas of the hypothalamus, father males had significant DECREASES in activation compared to the virgins. This was also consistent in the VNO itself, where virgin males had much higher c-Fos activation than fathers when exposed to pups.

So it looks like high activation in these areas is associated with aggressive behavior, while lower activation is associated with fathering behavior. But in order to prove this, you have to change the variables. In this case, the authors got rid of the VNO (a process called ablation). In VNO ablated mice, there is no VNO signal. And the VNO ablated mice immediately became very devoted fathers.

You can see above the parental scores for the VNO ablated mice vs sham operated mice. All the mice were virgin males, but those without a VNO were just as fatherly as experienced fathers! This suggests that the high signals from the VNO (detected by the c-Fos staining) are necessary for the AGGRESSIVE behaviors in virgin mice, and losing those signals is what produces fatherly behavior. This means that, in the VNO, the “smell” associated with pups may naturally be aversive, and is overcome by fatherhood. It’s a LACK of response that helps turn the angry males into protective fathers.

This is an intriguing thing to think about, and it raises more questions than it answers. HOW does exposure to a female reduce the response of the VNO? What is she releasing, or he experiencing, to changing the signaling and the behavior? It will be interesting to see if we can find the signals that turn hypermasculine males into protective fathers. This could tell us a lot about parenting in rodents and other mammals. Though, since, as far as we can tell, humans have no VNO, we’ll probably never make it into a cologne.