Dopamine and the Bruce Effect

If you take a recently impregnated female mouse and place her in a cage with an unfamiliar male, something curious often happens. The female, upon smelling the new male's urine, spontaneously aborts the fetus as her body drastically reduces its production of prolactin (PRL), a hormone responsible for progesterone secretion and thus essential to maintaining a pregnancy. The embryo fails to implant and the female begins ovulating again, making her receptive to copulation attempts by the new male. This strange phenomenon was first noticed by biologist Hilda Margaret Bruce in 1959, and is referred to as the Bruce effect.

The Bruce effect has been a curiosity to biologists since its discovery, as many have sought to explain why the female mouse’s body would seemingly be programmed to destroy her own offspring. After all, isn’t reproduction supposed to be the “goal” of evolution, and thus of life?

Several explanations have been offered to make sense of the Bruce effect. One is that it is an adaptive mechanism to protect the female’s potential maternal investment from being lost to infanticide. Infanticide is a fairly common practice among many species, and is usually committed by the male.

A male often cannot visibly determine if a female is pregnant when he encounters her (if her fertilization has been recent). Thus, upon copulating with her, he takes a risk that she may already be pregnant. If she were to produce offspring from another male, he might mistake them for his own and invest his resources in raising them (whatever “raising” may mean in the particular species). The risk being, if they are not his offspring he makes the investment but does not gain the benefit of his genes being passed on to a new generation. This is evolutionary suicide, and some biologists believe the males of many species instinctually go to great lengths to avoid it.

One way to make sure none of one’s resources go to raising another’s offspring is to simply get rid of the offspring. Male mice will frequently be infanticidal for the first three weeks after copulating with a female. Then they act paternally for about two months, after which they regress to their infanticidal tendencies. Coincidentally (not really), the mouse gestation period is three weeks and the weaning period is about two months. So the male times his infanticidal behavior perfectly to ensure that any offspring he helps to wean are his (note again that this is instinctual, not conscious behavior).

So, many biologists have suggested the Bruce effect may be a way for the female to avoid going through a pregnancy and investing all of her resources in it, just to have her progeny killed by a new male. Instead, she can abort the fetus and be receptive to him, in the process ensuring that she will have the opportunity to raise offspring into adulthood.

An alternative explanation for the Bruce effect involves mate selection. In this hypothesis, blocking the pregnancy is beneficial to the female by providing her with a novel mating partner. In highly territorial animals like rodents, a female may be more inclined to mate with the mouse whose urine she can currently smell, as he is most likely dominant in that territory.

Whatever the reason for the effect, a female also seems to reach a point when she has too much invested in the pregnancy already for it to be beneficial to abort. In mice, this occurs after the first few days of pregnancy, when the embryo becomes implanted. After this point, the Bruce effect no longer occurs. This is thought to involve a type of evolutionary weighing of the pros and cons. After three days of pregnancy, the female “decides” she has put enough time into her fetus that it would be counter-productive to start over. She must take the risk.

While the evolutionary cause of the Bruce effect may not be known for some time, a study published in July's Nature Neuroscience brings us closer to understanding the neural mechanism behind it. It seems to be dependent upon the versatile neurotransmitter dopamine.

When the female mouse smells another male’s urine, two sense organs in the nasal cavity are involved in processing the scent. One, called the vomeronasal organ (VNO), has pheromone-sensing capabilities. The other, the main olfactory epithelium (MOE), detects odorants. Both organs project fibers to the main olfactory bulb (MOB) and accessory olfactory bulb (AOB). The MOB contains a large population of dopaminergic interneurons, known as the juxtaglomerular dopaminergic interneurons (JGD).

As these dopamine interneurons are highly involved with olfaction, the scientists involved in the study wondered if they might also play a role in blocking pregnancy through urine odor detection. When they measured dopamine levels in the female mouse brain, they found a surge in dopamine occurred after the third day of the pregnancy—the time at which male odor no longer has an abortive effect on the fetus.

When they administered a dopamine antagonist, which blocks dopamine transmission, spontaneous abortion again occurred, even after implantation on the third day. Therefore, dopamine appears to interfere with the perception of the male urine odors, and is responsible for the suppression of the Bruce effect after the third day of a mouse pregnancy.

These findings represent a new understanding of the roles of the olfactory bulb, implicating it in the control of reproduction and social behavior in rodents. While not really applicable to humans, making sense of the Bruce effect is important in comprehending social behavior that, without knowledge of evolutionary theory, seems otherwise inexplicable.

Che Serguera, Viviana Triaca, Jakki Kelly-Barrett, Mumna Al Banchaabouchi, Liliana Minichiello (2008). Increased dopamine after mating impairs olfaction and prevents odor interference with pregnancy Nature Neuroscience, 11 (8), 949-956 DOI:10.1038/nn.2154