Israeli Researchers Suggest Repeated Miscarriages May be Tied to Olfactory System

Many women aren’t even aware of the fact that about half of all conceptions and some 15% of human pregnancies end in spontaneous miscarriage. Thus, when an embryo is conceived and a healthy baby is born, it is quite a miracle.  

In 1959, a British zoologist named Hilda Margaret Bruce discovered an unusual behavior in many species of rodents.

Studying sexual behavior I and estrus (“going into heat”) synchronization in lab mice, she housed newly mated pregnant females with male mice that were not the father of the carried embryo. When pregnant mice are exposed to the body-odor of a male that did not father the pregnancy, they almost always abort. As a result, the rate of miscarriages increased, and these females subsequently returning to estrus and mating with the new male. This behavior was named the Bruce effect in her honor 

Why this occurs is not fully understood, but the hypothesis is that the female “chooses” to miscarry because the chemical message is that a new, “more fit” male is available. Ethical considerations obviously prevented the researchers from repeating the Bruce experiments in humans. 

Now, researchers at the Weizmann Institute of Science in Rehovot say that understanding the connection could lead to a new search for the causes of unexplained spontaneous miscarriage in humans.

The odors we give off are a sort of body language – one that may affect our relationships more than we realize. Prof. Noam Sobel, head of Weizmann’s neurobiology department and his team wrote in the journal eLife that this “chemical communication” may extend to human reproduction as well. He found that women who suffer from a condition known as unexplained repeated pregnancy loss (uRPL) process messages concerning male body odor – especially their husband’s – in a different way than other women. These findings may point to new directions in the search for causes and prevention of this poorly understood disorder – as this could be a human variation of the Bruce effect. 

For the Bruce effect to occur in mice, the female must remember the body odor of the fathering male. To test for this in humans, the researchers presented participants with three odors – one extracted from a T-shirt worn by their spouse, and two from T-shirts worn other men.  They found that women with uRPL were able to identify their spouse by smell, while the control women could not. When retested with ordinary odorants to see if those with uRPL simply had a better sense of smell overall, they tested only marginally better. 

The ability of uRPL women to identify their spouse by smell was remarkable.

In another part of the experiment, in which the women did not know what odors they would be smelling, “several of these women said ‘oh, my husband’s in here’,” said research student Reut Weissgross, who co-lead the study. This never happened once with the control women.

Further testing suggested that these women are not just better at picking out the smell of their spouse, they may experience men’s body odor in a different way altogether. When asked to rate men’s body odors on various scales, including ranking them by standard scales for pleasantness and intensity, but also by such factors as fertility or sex appeal, the uRPL-affected women were unique in the way they described and graded the smells, and significantly different from control women in their answers.

In the final phase of the research, the experimenters used both structural and functional brain imaging to study these women. The structural imaging revealed that women with uRPL have smaller olfactory bulbs; these are the initial brain-relay for smell. Using functional imaging, they found an increased response to men’s body odors in the hypothalamus of the brains of women with uRPL. The hypothalamus plays a key role in the Bruce effect in mice; it is a region that participates, among other things, in coordinating pregnancy and overall hormonal regulation.

 “It seems these losses of pregnancy may be ‘unexplained’ because physicians are looking for problems in the uterus, when they should also be looking in the brain, and particularly the olfactory brain,” concluded Weissgross. Sobel cautioned, however, that “correlation is not causation, so our findings do not prove in any way that the olfactory system, or body odors, cause miscarriage. But our findings do point to a novel and potentially important direction for research in this poorly managed condition.”




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